2025
Wang., Z. A.; Markert, J.; Whedon, S. D.; Abeywardana, M. Y.; Sheng, X.; Nam, E.; Lee, K.; Chen, M.; Waterbury, A.; Zhao, Y.; Farnung, L.; Cole, P. A.
Structural and enzymatic plasticity of SIRT6 deacylase activity Journal Article
In: J. Biol. Chem., vol. 301, pp. 108446, 2025.
BibTeX | Tags:
@article{nokey,
title = {Structural and enzymatic plasticity of SIRT6 deacylase activity},
author = {Z. A. Wang. and J. Markert and S. D. Whedon and M. Y. Abeywardana and X. Sheng and E. Nam and K. Lee and M. Chen and A. Waterbury and Y. Zhao and L. Farnung and P. A. Cole},
year = {2025},
date = {2025-05-01},
journal = {J. Biol. Chem.},
volume = {301},
pages = {108446},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Iwase, R.; Maisonet, I. Jaen; Lee, K.; Buhrlage, S. J.; Cole, P. A.
Deubiquitinase processing of a non-natural linkage of ubiquitinated-PTEN. Journal Article
In: Bioorg. Chem., vol. 157, pp. 108223, 2025.
BibTeX | Tags:
@article{nokey,
title = {Deubiquitinase processing of a non-natural linkage of ubiquitinated-PTEN.},
author = {R. Iwase and I. Jaen Maisonet and K. Lee and S. J. Buhrlage and P. A. Cole },
year = {2025},
date = {2025-04-01},
journal = {Bioorg. Chem.},
volume = {157},
pages = {108223},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Xie, X.; Zhang, O.; Yeo, M. J. R.; Lee, C.; Tao, R.; Harry, S. A.; Payne, N. Connor; Nam, E.; Paul, L.; Li, Y.; Kwok, H. S.; Jiang, H.; Mao, H.; Hadley, J. L.; Lin, H.; Batts, M.; Gosavi, P. M.; D'Angiolella, V.; Cole, P. A.; Mazitschek, R.; Northcott, P. A.; Zheng, N.; Liau, B. B.
Converging mechanism of UM171 and KBTBD4 neomorphic cancer mutations Journal Article
In: Nature, vol. 639, pp. 241-249, 2025.
BibTeX | Tags:
@article{nokey,
title = {Converging mechanism of UM171 and KBTBD4 neomorphic cancer mutations},
author = {X. Xie and O. Zhang and M. J. R. Yeo and C. Lee and R. Tao and S. A. Harry and N. Connor Payne and E. Nam and L. Paul and Y. Li and H. S. Kwok and H. Jiang and H. Mao and J. L. Hadley and H. Lin and M. Batts and P. M. Gosavi and V. D'Angiolella and P. A. Cole and R. Mazitschek and P. A. Northcott and N. Zheng and B. B. Liau},
year = {2025},
date = {2025-02-12},
journal = {Nature},
volume = {639},
pages = {241-249},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Yeo, M. J. R.; Zhang, O.; Xie, X.; Nam, E.; Payne, N. Connor; Gosavi, P. M.; Kwok, H. S.; Iram, I.; Lee, C.; Li, J.; Chen, N. J.; Nguyen, K.; Jiang, H.; Wang, Z. A.; Lee, K.; Mao, H.; Harry, S. A.; Barakat, I. A.; Takahashi, M.; Waterbury, A. L.; Barone, M.; Mattevi, A.; Carr, S. A.; Udeshi, N. D.; Bar-Peled, L.; Cole, P. A.; Mazitschek, R.; Liau, B. B.; Zheng, N.
UM171 glues asymmetric CRL3-HDAC1/2 assembly to degrade CoREST corepressors Journal Article
In: Nature, vol. 639, pp. 232-240, 2025.
BibTeX | Tags:
@article{nokey,
title = {UM171 glues asymmetric CRL3-HDAC1/2 assembly to degrade CoREST corepressors},
author = {M. J. R. Yeo and O. Zhang and X. Xie and E. Nam and N. Connor Payne and P. M. Gosavi and H. S. Kwok and I. Iram and C. Lee and J. Li and N. J. Chen and K. Nguyen and H. Jiang and Z. A. Wang and K. Lee and H. Mao and S. A. Harry and I. A. Barakat and M. Takahashi and A. L. Waterbury and M. Barone and A. Mattevi and S. A. Carr and N. D. Udeshi and L. Bar-Peled and P. A. Cole and R. Mazitschek and B. B. Liau and N. Zheng },
year = {2025},
date = {2025-02-12},
journal = {Nature},
volume = {639},
pages = {232-240},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Liu, R.; Ren, X.; Park, Y. E.; Feng, H.; Sheng, X.; Song, X.; AminiTabrizi, R.; Shah, H.; Li, L.; Zhang, Y.; Abdullah, K. G.; Dubois-Coyne, S.; Lin, H.; Cole, P. A.; DeBerardinis, R. J.; McBrayer, S. K.; Huang, H.; Zhao, Yingming
Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis Journal Article
In: Cell Metab., vol. 37, iss. 2, pp. 377-394, 2025.
BibTeX | Tags:
@article{nokey,
title = {Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis},
author = {R. Liu and X. Ren and Y. E. Park and H. Feng and X. Sheng and X. Song and R. AminiTabrizi and H. Shah and L. Li and Y. Zhang and K. G. Abdullah and S. Dubois-Coyne and H. Lin and P. A. Cole and R. J. DeBerardinis and S. K. McBrayer and H. Huang and Yingming Zhao},
year = {2025},
date = {2025-02-04},
journal = {Cell Metab.},
volume = {37},
issue = {2},
pages = {377-394},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2024
Whedon, S. D.; Lee, K.; Wang, Z. A.; Zahn, E.; Lu, C.; Abeywardana, M. Y.; Fairall, L.; Nam, E.; DuBois-Coyne, S.; Ioannes, P De; Sheng, X.; Andrei, A.; Lundberg, E.; Jiang, J.; Armache, K. -J.; Zhao, Y.; Schwabe, J. W. R.; Wu, M.; Garcia, B. A.; Cole, P. A.
Circular Engineered Sortase for Interrogating Histone H3 in Chromatin Journal Article
In: J. Am. Chem. Soc., vol. 146, pp. 33914-33927, 2024.
BibTeX | Tags:
@article{nokey,
title = {Circular Engineered Sortase for Interrogating Histone H3 in Chromatin},
author = {S. D. Whedon and K. Lee and Z. A. Wang and E. Zahn and C. Lu and M. Y. Abeywardana and L. Fairall and E. Nam and S. DuBois-Coyne and P De Ioannes and X. Sheng and A. Andrei and E. Lundberg and J. Jiang and K.-J. Armache and Y. Zhao and J.W. R. Schwabe and M. Wu and B. A. Garcia and P. A. Cole},
year = {2024},
date = {2024-11-25},
urldate = {2024-11-25},
journal = {J. Am. Chem. Soc.},
volume = {146},
pages = {33914-33927},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Wandrey, N.; Hamilton, L.; Boley, J.; Haynes, A.; Redinger, M.; Hill, M.; Hagemeister, M.; Cole, P. A.; Moxley, M. A.; Thomas, A. A.
AANAT kinetics of CoASH-targeted electrophiles of tryptamine and related analogs. Journal Article
In: Bioorg. Med. Chem. Lett ., vol. 113, pp. 129975, 2024.
BibTeX | Tags:
@article{nokey,
title = {AANAT kinetics of CoASH-targeted electrophiles of tryptamine and related analogs.},
author = {N. Wandrey and L. Hamilton and J. Boley and A. Haynes and M. Redinger and M. Hill and M. Hagemeister and P. A. Cole and M. A. Moxley and A. A. Thomas},
year = {2024},
date = {2024-11-15},
journal = {Bioorg. Med. Chem. Lett .},
volume = {113},
pages = {129975},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cao, R.; Gozlan, O.; Airich, A.; Tveriakhina, L.; Zhou, H.; Jiang, H.; Cole, P. A.; Aster, J. C.; Klein, T.; Sprinzak, D.; Blacklow, S. C.
Structural requirements for activity of Mind bomb1 in Notch signaling Journal Article
In: Structure, vol. 32, iss. 10, pp. 1667-1676, 2024.
BibTeX | Tags:
@article{nokey,
title = {Structural requirements for activity of Mind bomb1 in Notch signaling},
author = {R. Cao and O. Gozlan and A. Airich and L. Tveriakhina and H. Zhou and H. Jiang and P. A. Cole and J. C. Aster and T. Klein and D. Sprinzak and S. C. Blacklow},
year = {2024},
date = {2024-10-03},
journal = {Structure},
volume = {32},
issue = {10},
pages = {1667-1676},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Yapa-Abeywardana, M.; Whedon, S. D.; Lee, K.; Nam, E.; Dovarganes, R.; DuBois-Coyne, S.; Haque, I. A.; Wang, Z. A; Cole, P. A.
Multifaceted regulation of sirtuin 2 (Sirt2) deacetylase activity Journal Article
In: J. Biol. Chem., vol. 300, no. 107722, 2024.
BibTeX | Tags:
@article{nokey,
title = {Multifaceted regulation of sirtuin 2 (Sirt2) deacetylase activity},
author = {M. Yapa-Abeywardana and S. D. Whedon and K. Lee and E. Nam and R. Dovarganes and S. DuBois-Coyne and I. A. Haque and Z. A Wang and P. A. Cole},
year = {2024},
date = {2024-08-28},
journal = {J. Biol. Chem.},
volume = {300},
number = {107722},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Waddell, A.; Grbic, N.; Leibowitz, K.; Wyant, W. A.; Choudhury, S.; Park, K.; Collard, M.; Cole, P. A.; Alani, R. M.
p300 KAT regulates SOX10 stability and function in human melanoma Journal Article
In: Cancer Res. Commun., vol. 4, iss. 8, pp. 1894-1907, 2024.
BibTeX | Tags:
@article{nokey,
title = {p300 KAT regulates SOX10 stability and function in human melanoma},
author = {A. Waddell and N. Grbic and K. Leibowitz and W. A. Wyant and S. Choudhury and K. Park and M. Collard and P. A. Cole and R. M. Alani},
year = {2024},
date = {2024-08-01},
journal = {Cancer Res. Commun.},
volume = {4},
issue = {8},
pages = {1894-1907},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Jiang, H.; Miller, B. D.; Viennet, T.; Kim, H.; Lee, K.; Arthanari, H.; Cole, P. A.
Protein Semisynthesis Reveals Plasticity in HECT E3 Ubiquitin Ligase Mechanisms Journal Article
In: Nat. Chem., vol. In Press, 2024.
@article{nokey,
title = {Protein Semisynthesis Reveals Plasticity in HECT E3 Ubiquitin Ligase Mechanisms},
author = {H. Jiang and B. D. Miller and T. Viennet and H. Kim and K. Lee and H. Arthanari and P. A. Cole},
doi = {https://doi.org/10.1038/s41557-024-01576-z},
year = {2024},
date = {2024-07-19},
journal = {Nat. Chem.},
volume = {In Press},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lee, K.; Barone, M.; Waterbury, A. L.; Jiang, H.; Nam, E.; DuBois-Coyne, S. E.; Whedon, S. D.; Wang, Z. A.; Caroli, J.; Neal, K.; Ibeabuchi, B.; Dhoondia, Z.; Kuroda, M. I.; Liau, B. B.; Beck, S.; Mattevi, A.; Cole, P. A.
Uncoupling Histone Modification Crosstalk by Engineering Lysine Demethylase LSD1 Journal Article
In: Nat. Chem. Biol., 2024.
@article{nokey,
title = {Uncoupling Histone Modification Crosstalk by Engineering Lysine Demethylase LSD1},
author = {K. Lee and M. Barone and A. L. Waterbury and H. Jiang and E. Nam and S. E. DuBois-Coyne and S. D. Whedon and Z. A. Wang and J. Caroli and K. Neal and B. Ibeabuchi and Z. Dhoondia and M. I. Kuroda and B. B. Liau and S. Beck and A. Mattevi and P. A. Cole },
doi = {https://doi.org/10.1038/s41589-024-01671-9},
year = {2024},
date = {2024-07-04},
urldate = {2024-07-04},
journal = {Nat. Chem. Biol.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Smolko, A. E.; Sullivan, D. W.; Olsen, S. N.; Kang, H.; Whedon, S. D.; Baell, J. B.; Cole, P. A.; Armstrong, S. A.; Kuroda, M. I.
A MOZ-TIF2 leukemia mouse model displays KAT6-dependent H3K23 propionylation and overexpression of a set of active developmental genes Journal Article
In: Proc. Natl. Acad. Sci. U. S. A., vol. 121, iss. 26, no. e2405905121, 2024.
BibTeX | Tags:
@article{nokey,
title = {A MOZ-TIF2 leukemia mouse model displays KAT6-dependent H3K23 propionylation and overexpression of a set of active developmental genes},
author = {A. E. Smolko and D. W. Sullivan and S. N. Olsen and H. Kang and S. D. Whedon and J. B. Baell and P. A. Cole and S. A. Armstrong and M. I. Kuroda},
year = {2024},
date = {2024-06-25},
urldate = {2024-06-25},
journal = {Proc. Natl. Acad. Sci. U. S. A.},
volume = {121},
number = {e2405905121},
issue = {26},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Waterbury, A. L.; Kwok, H. S.; Lee, C.; Narducci, D. N.; Freedy, A. M.; Su, C.; Raval, S.; Reiter, A. H.; Hawkins, W.; Lee, K.; Li, J.; Hoenig, S. M; Vinyard, M. E.; Cole, P. A.; Hansen, A. S.; Carr, S. A.; Papanastasiou, M.; Liau, B. B.
An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing Journal Article
In: Mol. Cell, vol. 84, iss. 12, pp. 2238-2254, 2024.
BibTeX | Tags:
@article{nokey,
title = {An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing},
author = {A. L. Waterbury and H. S. Kwok and C. Lee and D. N. Narducci and A. M. Freedy and C. Su and S. Raval and A. H. Reiter and W. Hawkins and K. Lee and J. Li and S. M Hoenig and M. E. Vinyard and P. A. Cole and A. S. Hansen and S. A. Carr and M. Papanastasiou and B. B. Liau},
year = {2024},
date = {2024-06-20},
urldate = {2024-06-20},
journal = {Mol. Cell},
volume = {84},
issue = {12},
pages = {2238-2254},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Geethadevi, A.; Collard, M.; Findlay, T.; Deng, Y.; Fisher, R.; Vaidya, N.; Eberhart, C.; Cole, P. A.; Alani, R.; Rubens, J.; Raabe, E.
Selective inhibition of the CoREST complex as a novel therapeutic target of atypical teratoid rhabdoid tumors Journal Article
In: Cancer Res., vol. 84, no. 7555, 2024.
BibTeX | Tags:
@article{nokey,
title = {Selective inhibition of the CoREST complex as a novel therapeutic target of atypical teratoid rhabdoid tumors},
author = {A. Geethadevi and M. Collard and T. Findlay and Y. Deng and R. Fisher and N. Vaidya and C. Eberhart and P. A. Cole and R. Alani and J. Rubens and E. Raabe},
year = {2024},
date = {2024-03-22},
journal = {Cancer Res.},
volume = {84},
number = {7555},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Wright, K. M.; Nathan, S.; Jiang, H.; Xia, W.; Kim, H.; Chakouri, N.; Nwafor, J. N.; Fossier, L.; Srinivasan, L.; Chen, Z.; Boronina, T.; Post, J.; Paul, S.; Cole, R. N.; Ben-Johny, M.; Cole, P. A.; Gabelli, S. B.
NEDD4L Intramolecular Interactions Regulate Its Auto- and Substrate NaV1.5 Ubiquitination. Journal Article
In: J. Biol. Chem., vol. 300, pp. 105715, 2024.
@article{nokey,
title = {NEDD4L Intramolecular Interactions Regulate Its Auto- and Substrate NaV1.5 Ubiquitination.},
author = {K. M. Wright and S. Nathan and H. Jiang and W. Xia and H. Kim and N. Chakouri and J. N. Nwafor and L. Fossier and L. Srinivasan and Z. Chen and T. Boronina and J. Post and S. Paul and R. N. Cole and M. Ben-Johny and P. A. Cole and S. B. Gabelli},
doi = {https://doi.org/10.1016/j.jbc.2024.105715},
year = {2024},
date = {2024-03-01},
urldate = {2024-03-01},
journal = {J. Biol. Chem.},
volume = {300},
pages = {105715},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Wu, M.; Hanly, A.; Gibson, F.; Fisher, R.; Rogers, S.; Park, K.; Zuger, A.; Kuang, K.; Kalin, J. H.; Nocco, S.; Cole, M.; Xiao, A.; Agus, F.; Labadorf, A.; Beck, S.; Collard, M.; Cole, P. A.; Alani., R. M.
The CoREST Repressor Complex Mediates Phenotype Switching and Therapy Resistance in Melanoma. Journal Article
In: J. Clin. Invest., pp. e171063, 2024.
@article{nokey,
title = {The CoREST Repressor Complex Mediates Phenotype Switching and Therapy Resistance in Melanoma.},
author = {M. Wu and A. Hanly and F. Gibson and R. Fisher and S. Rogers and K. Park and A. Zuger and K. Kuang and J. H. Kalin and S. Nocco and M. Cole and A. Xiao and F. Agus and A. Labadorf and S. Beck and M. Collard and P. A. Cole and R. M. Alani.},
doi = {10.1172/JCI171063},
year = {2024},
date = {2024-02-01},
journal = {J. Clin. Invest.},
pages = {e171063},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hagemeister, M.; Hamilton, L.; Wandrey, N.; Hill, M.; Mounce, E.; Mosel, N.; Lytle, K.; Redinger, M.; Boley, J.; Fancher, N.; Haynes, A.; Fill, I.; Cole, P. A.; Hill, E.; Moxley, M. A.; Thomas, A. A.
Evaluation of Rhodanine Indolinones as AANAT Inhibitors Journal Article
In: ChemMedChem, vol. 19, pp. e202300567, 2024.
@article{nokey,
title = {Evaluation of Rhodanine Indolinones as AANAT Inhibitors},
author = {M. Hagemeister and L. Hamilton and N. Wandrey and M. Hill and E. Mounce and N. Mosel and K. Lytle and M. Redinger and J. Boley and N. Fancher and A. Haynes and I. Fill and P. A. Cole and E. Hill and M. A. Moxley and A. A. Thomas},
doi = {10.1002/cmdc.202300567},
year = {2024},
date = {2024-01-02},
urldate = {2024-01-02},
journal = {ChemMedChem},
volume = {19},
pages = {e202300567},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Kida, M.; Fatima, I.; Otero-Viñas, E. Rozhkova M.; Wu, M.; Kalin, J. H.; Cole, P. A.; Falanga, V.; Alani, R. M.; Sharov, A. A.
Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration Journal Article
In: J. Invest. Dermatol., vol. 144, pp. 378-386, 2024.
@article{nokey,
title = {Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration},
author = {M. Kida and I. Fatima and E. Rozhkova M. Otero-Viñas and M. Wu and J. H. Kalin and P. A. Cole and V. Falanga and R. M. Alani and A. A. Sharov},
doi = {10.1016/j.jid.2023.07.022},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {J. Invest. Dermatol.},
volume = {144},
pages = {378-386},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2023
Wright, K. M.; Jiang, H.; Xia, W.; Murphy, M. B.; Boronina, T. N.; Nwafor, J. N.; Kim, H.; Iheanacho, A. M.; Azurmendi, P. A.; Cole, R. N.; Cole, P. A.; Gabelli, S. B.
The C-Terminal of NaV1.7 Is Ubiquitinated by NEDD4L. Journal Article
In: ACS Bio. Med. Chem. Au, vol. 3, pp. 516-527, 2023.
@article{nokey,
title = {The C-Terminal of NaV1.7 Is Ubiquitinated by NEDD4L.},
author = {K. M. Wright and H. Jiang and W. Xia and M. B. Murphy and T. N. Boronina and J. N. Nwafor and H. Kim and A. M. Iheanacho and P. A. Azurmendi and R. N. Cole and P. A. Cole and S. B. Gabelli},
doi = {10.1021/acsbiomedchemau.3c00031},
year = {2023},
date = {2023-10-13},
journal = {ACS Bio. Med. Chem. Au},
volume = {3},
pages = {516-527},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mansur, A.; Joseph, R.; Kim, E. S.; Jean-Beltran, P. M.; Udeshi, N. D.; Pearce, C.; Jiang, H.; Iwase, R.; Milev, M. P.; Almousa, H. A.; McNamara, E.; Widrick, J.; Perez, C.; Ravenscroft, G.; Sacher, M.; Cole, P. A.; Carr, S. A.; Gupta, V. A.
Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset Journal Article
In: Elife, vol. 12, pp. e81966, 2023.
@article{nokey,
title = {Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset},
author = {A. Mansur and R. Joseph and E. S. Kim and P. M. Jean-Beltran and N. D. Udeshi and C. Pearce and H. Jiang and R. Iwase and M. P. Milev and H. A. Almousa and E. McNamara and J. Widrick and C. Perez and G. Ravenscroft and M. Sacher and P. A. Cole and S. A. Carr and V. A. Gupta},
doi = {10.7554/eLife.81966},
year = {2023},
date = {2023-07-11},
urldate = {2023-07-11},
journal = {Elife},
volume = {12},
pages = {e81966},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nardone, C.; Palanski, B. A.; Scott, D. C.; Timms, R. T.; Barber, K. W.; Gu, X.; Mao, A.; Leng, Y.; Watson, E. V.; Schulman, B. A.; Cole, P. A.; Elledge, S. J.
A central role for regulated protein stability in the control of TFE3 and MITF by nutrients Journal Article
In: Mol. Cell, vol. 83, pp. 57-73, 2023.
@article{1665792,
title = {A central role for regulated protein stability in the control of TFE3 and MITF by nutrients},
author = {C. Nardone and B. A. Palanski and D. C. Scott and R. T. Timms and K. W. Barber and X. Gu and A. Mao and Y. Leng and E. V. Watson and B. A. Schulman and P. A. Cole and S. J. Elledge},
url = {https://www.sciencedirect.com/science/article/pii/S1097276522011704?via%3Dihub},
year = {2023},
date = {2023-01-01},
journal = {Mol. Cell},
volume = {83},
pages = {57-73},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Wang, Z. A.; Markert, J. W.; Whedon, S. D.; Yapa-Abeywardana, M.; Lee, K.; Jiang, H.; Suarez, C.; Li, H.; Farnung, L.; Cole, P. A.
Structural Basis of Sirtuin 6-Catalyzed Nucleosome Deacetylation Journal Article
In: J. Am. Chem. Soc., vol. 145, pp. 6811-6822, 2023.
BibTeX | Tags:
@article{Wang2023,
title = {Structural Basis of Sirtuin 6-Catalyzed Nucleosome Deacetylation},
author = {Z. A. Wang and J. W. Markert and S. D. Whedon and M. Yapa-Abeywardana and K. Lee and H. Jiang and C. Suarez and H. Li and L. Farnung and P. A. Cole},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {J. Am. Chem. Soc.},
volume = {145},
pages = {6811-6822},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Iwase, R.; Dempsey, D. R.; Whedon, S. D.; Jiang, H.; Palanski, B. A.; Deng, B.; Cole, P. A.
Semisynthetic Approach to the Analysis of Tumor Suppressor PTEN Ubiquitination Journal Article
In: J. Am. Chem. Soc., vol. 145, pp. 6039–6044, 2023.
@article{1684906,
title = {Semisynthetic Approach to the Analysis of Tumor Suppressor PTEN Ubiquitination},
author = {R. Iwase and D. R. Dempsey and S. D. Whedon and H. Jiang and B. A. Palanski and B. Deng and P. A. Cole},
url = {https://pubs.acs.org/doi/abs/10.1021/jacs.2c13871},
year = {2023},
date = {2023-01-01},
journal = {J. Am. Chem. Soc.},
volume = {145},
pages = {6039–6044},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2022
Lee, K.; Whedon, S. D.; Wang, Z. A.; Cole, P. A.
Distinct biochemical properties of the class I histone deacetylase complexes Journal Article
In: Curr. Opin. Chem. Biol., vol. 70, pp. 102179, 2022.
BibTeX | Tags:
@article{1650158,
title = {Distinct biochemical properties of the class I histone deacetylase complexes},
author = {K. Lee and S. D. Whedon and Z. A. Wang and P. A. Cole},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Curr. Opin. Chem. Biol.},
volume = {70},
pages = {102179},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Jiang, H.; Chiang, C.; Chen, Z.; Nathan, S.; D’Agostino, G.; Paulo, J.; Song, G.; Zhu, H.; Gabelli, S. B.; Cole, P. A.
Enzymatic Analysis of WWP2 E3 Ubiquitin Ligase Using Protein Microarrays Identifies Autophagy-Related Substrates Journal Article
In: J. Biol. Chem., vol. 298, pp. 101854, 2022.
BibTeX | Tags:
@article{1650156,
title = {Enzymatic Analysis of WWP2 E3 Ubiquitin Ligase Using Protein Microarrays Identifies Autophagy-Related Substrates},
author = {H. Jiang and C. Chiang and Z. Chen and S. Nathan and G. D’Agostino and J. Paulo and G. Song and H. Zhu and S. B. Gabelli and P. A. Cole},
year = {2022},
date = {2022-01-01},
journal = {J. Biol. Chem.},
volume = {298},
pages = {101854},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bae, H.; Viennet, T.; Park, E.; Chu, N.; Salguero, A.; Eck, M. J.; Arthanari, H.; Cole, P. A.
PH domain-mediated autoinhibition and oncogenic activation of Akt Journal Article
In: eLife, vol. 11, pp. e80148, 2022.
BibTeX | Tags:
@article{1650157,
title = {PH domain-mediated autoinhibition and oncogenic activation of Akt},
author = {H. Bae and T. Viennet and E. Park and N. Chu and A. Salguero and M. J. Eck and H. Arthanari and P. A. Cole},
year = {2022},
date = {2022-01-01},
journal = {eLife},
volume = {11},
pages = {e80148},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Min, D.; Byun, J.; Lee, E. H.; Khan, A. A.; Liu, C.; Loudig, O.; Hu, W.; Zhao, Y.; Herlyn, M.; Tycko, B.; Cole, P. A.; Ryu, B.
Epigenetic Silencing of BMP6 by Sin3A-HDAC1/2 Repressor Complex Drives Melanoma Metastasis via FAM83G/PAWS1 Journal Article
In: Mol. Cancer Res., vol. 20, pp. 217-230, 2022.
BibTeX | Tags:
@article{1624374,
title = {Epigenetic Silencing of BMP6 by Sin3A-HDAC1/2 Repressor Complex Drives Melanoma Metastasis via FAM83G/PAWS1},
author = {D. Min and J. Byun and E. H. Lee and A. A. Khan and C. Liu and O. Loudig and W. Hu and Y. Zhao and M. Herlyn and B. Tycko and P. A. Cole and B. Ryu},
year = {2022},
date = {2022-01-01},
journal = {Mol. Cancer Res.},
volume = {20},
pages = {217-230},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Wang, Z. A.; Whedon, S. D.; Wu, M.; Weng, S.; Brown, E. A.; Anmangandla, A.; Regan, L.; Lee, K.; Du, J.; Hong, J. Y.; Fairall, L.; Kay, T.; Lin, H.; Zhao, Y.; Schwabe, J. W. R.; Cole, P. A.
Histone H2B Deacylation Selectivity: Exploring Chromatin’s Dark Matter with an Engineered Sortase Journal Article
In: J. Am. Chem. Soc., vol. 144, pp. 3360-3364, 2022.
BibTeX | Tags:
@article{1650155,
title = {Histone H2B Deacylation Selectivity: Exploring Chromatin’s Dark Matter with an Engineered Sortase},
author = {Z. A. Wang and S. D. Whedon and M. Wu and S. Weng and E. A. Brown and A. Anmangandla and L. Regan and K. Lee and J. Du and J. Y. Hong and L. Fairall and T. Kay and H. Lin and Y. Zhao and J. W. R. Schwabe and P. A. Cole},
year = {2022},
date = {2022-01-01},
journal = {J. Am. Chem. Soc.},
volume = {144},
pages = {3360-3364},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Whedon, S. D.; Cole, P. A.
KATs off: Biomedical insights from lysine acetyltransferase inhibitors Journal Article
In: Curr. Opin. Chem. Biol., vol. 72, pp. 102255, 2022.
@article{1665791,
title = {KATs off: Biomedical insights from lysine acetyltransferase inhibitors},
author = {S. D. Whedon and P. A. Cole},
url = {https://www.sciencedirect.com/science/article/pii/S1367593122001405?via%3Dihub},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Curr. Opin. Chem. Biol.},
volume = {72},
pages = {102255},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Salguero, A.; Chen, M.; Balana, A.; Chu, N.; Jiang, H.; Bae, H.; Palanski, B. A.; Wright, K.; Nathan, S.; H.Zhu,; Gabelli, S.; Pratt, M.; Cole, P. A.
Multifaceted Regulation of Akt by Diverse C-terminal Post-translational Modifications Journal Article
In: ACS Chem. Biol., vol. 17, pp. 68-76, 2022.
BibTeX | Tags:
@article{1624376,
title = {Multifaceted Regulation of Akt by Diverse C-terminal Post-translational Modifications},
author = {A. Salguero and M. Chen and A. Balana and N. Chu and H. Jiang and H. Bae and B. A. Palanski and K. Wright and S. Nathan and H.Zhu and S. Gabelli and M. Pratt and P. A. Cole},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {ACS Chem. Biol.},
volume = {17},
pages = {68-76},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2021
Shiota, H.; Alekseyenko, A. A.; Wang, Z. A; Filic, I.; Knox, T. M.; Luong, N. M.; Huang, Y.; Scott, D. A.; Jones, K. L.; Gokhale, P. C.; Lemieux, M. E.; Cole, P. A.; Kuroda, M. I.; French, C. A.
In: Mol. Cancer Res., vol. 19, no. 11, pp. 1818-1830, 2021, ISSN: 1557-3125.
Abstract | Links | BibTeX | Tags:
@article{1624366,
title = {Chemical Screen Identifies Diverse and Novel Histone Deacetylase Inhibitors as Repressors of NUT Function: Implications for NUT Carcinoma Pathogenesis and Treatment},
author = {H. Shiota and A. A. Alekseyenko and Z. A Wang and I. Filic and T. M. Knox and N. M. Luong and Y. Huang and D. A. Scott and K. L. Jones and P. C. Gokhale and M. E. Lemieux and P. A. Cole and M. I. Kuroda and C. A. French},
doi = {10.1158/1541-7786.MCR-21-0259},
issn = {1557-3125},
year = {2021},
date = {2021-11-01},
urldate = {2021-11-01},
journal = {Mol. Cancer Res.},
volume = {19},
number = {11},
pages = {1818-1830},
abstract = {NUT carcinoma (NC), characterized most commonly by the BRD4-NUTM1 fusion, is a rare, aggressive variant of squamous carcinoma with no effective treatment. BRD4-NUT drives growth and maintains the poorly differentiated state of NC by activating pro-growth genes such as MYC, through the formation of massive, hyperacetylated, superenhancer-like domains termed megadomains. BRD4-NUT-mediated hyperacetylation of chromatin is facilitated by the chromatin-targeting tandem bromodomains of BRD4, combined with NUT, which recruits the histone acetyltransferase, p300. Here, we developed a high-throughput small-molecule screen to identify inhibitors of transcriptional activation by NUT. In this dCAS9-based GFP-reporter assay, the strongest hits were diverse histone deacetylase (HDAC) inhibitors. Two structurally unrelated HDAC inhibitors, panobinostat and the novel compound, IRBM6, both repressed growth and induced differentiation of NC cells in proportion to their inhibition of NUT transcriptional activity. These two compounds repressed transcription of megadomain-associated oncogenic genes, such as MYC and SOX2, while upregulating pro-differentiation, non-megadomain-associated genes, including JUN, FOS, and key cell-cycle regulators, such as CDKN1A. The transcriptional changes correlate with depletion of BRD4-NUT from megadomains, and redistribution of the p300/CBP-associated chromatin acetylation mark, H3K27ac, away from megadomains toward regular enhancer regions previously populated by H3K27ac. In NC xenograft models, we demonstrated that suppression of tumor growth by panobinostat was comparable with that of bromodomain inhibition, and when combined they improved both survival and growth suppression. IMPLICATIONS: The findings provide mechanistic and preclinical rationale for the use of HDAC inhibitors, alone or combined with other agents, in the treatment of NUT carcinoma.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dempsey, D. R.; Viennet, T.; Iwase, R.; Park, E. Y.; Henriquez, S.; Chen, Z.; Jeliazkov, J. R.; Palanski, B. A.; Phan, K. L.; Coote, P.; Gray, J. J.; Eck, M. J.; Gabelli, S. B.; Arthanari, H.; Cole, P. A.
The structural basis of PTEN regulation by multi-site phosphorylation Journal Article
In: Nat. Struct. Mol. Biol., vol. 28, no. 10, pp. 858-868, 2021, ISSN: 1545-9985.
Abstract | Links | BibTeX | Tags: Animals, Ciona intestinalis, Crystallography, Fluorescence Polarization, Humans, Magnetic Resonance Spectroscopy, Molecular Docking Simulation, Phosphorylation, PTEN Phosphohydrolase, X-Ray
@article{1624365,
title = {The structural basis of PTEN regulation by multi-site phosphorylation},
author = {D. R. Dempsey and T. Viennet and R. Iwase and E. Y. Park and S. Henriquez and Z. Chen and J. R. Jeliazkov and B. A. Palanski and K. L. Phan and P. Coote and J. J. Gray and M. J. Eck and S. B. Gabelli and H. Arthanari and P. A. Cole},
doi = {10.1038/s41594-021-00668-5},
issn = {1545-9985},
year = {2021},
date = {2021-10-28},
urldate = {2021-10-28},
journal = {Nat. Struct. Mol. Biol.},
volume = {28},
number = {10},
pages = {858-868},
abstract = {Phosphatase and tensin homolog (PTEN) is a phosphatidylinositol-3,4,5-triphosphate (PIP3) phospholipid phosphatase that is commonly mutated or silenced in cancer. PTEN’s catalytic activity, cellular membrane localization and stability are orchestrated by a cluster of C-terminal phosphorylation (phospho-C-tail) events on Ser380, Thr382, Thr383 and Ser385, but the molecular details of this multi-faceted regulation have remained uncertain. Here we use a combination of protein semisynthesis, biochemical analysis, NMR, X-ray crystallography and computational simulations on human PTEN and its sea squirt homolog, VSP, to obtain a detailed picture of how the phospho-C-tail forms a belt around the C2 and phosphatase domains of PTEN. We also visualize a previously proposed dynamic N-terminal α-helix and show that it is key for PTEN catalysis but disordered upon phospho-C-tail interaction. This structural model provides a comprehensive framework for how C-tail phosphorylation can impact PTEN’s cellular functions.},
keywords = {Animals, Ciona intestinalis, Crystallography, Fluorescence Polarization, Humans, Magnetic Resonance Spectroscopy, Molecular Docking Simulation, Phosphorylation, PTEN Phosphohydrolase, X-Ray},
pubstate = {published},
tppubtype = {article}
}
Huang, H.; Zhang, D.; Weng, Y.; Delaney, K.; Tang, Z.; Yan, C.; Qi, S.; Peng, C.; Cole, P. A.; Roeder, R. G.; Zhao, Y.
The regulatory enzymes and protein substrates for the lysine β-hydroxybutyrylation pathway Journal Article
In: Sci. Adv., vol. 7, no. 9, 2021, ISSN: 2375-2548.
Abstract | Links | BibTeX | Tags:
@article{1624369,
title = {The regulatory enzymes and protein substrates for the lysine β-hydroxybutyrylation pathway},
author = {H. Huang and D. Zhang and Y. Weng and K. Delaney and Z. Tang and C. Yan and S. Qi and C. Peng and P. A. Cole and R. G. Roeder and Y. Zhao},
doi = {10.1126/sciadv.abe2771},
issn = {2375-2548},
year = {2021},
date = {2021-02-01},
urldate = {2021-02-01},
journal = {Sci. Adv.},
volume = {7},
number = {9},
abstract = {Metabolism-mediated epigenetic changes represent an adapted mechanism for cellular signaling, in which lysine acetylation and methylation have been the historical focus of interest. We recently discovered a β-hydroxybutyrate-mediated epigenetic pathway that couples metabolism to gene expression. However, its regulatory enzymes and substrate proteins remain unknown, hindering its functional study. Here, we report that the acyltransferase p300 can catalyze the enzymatic addition of β-hydroxybutyrate to lysine (Kbhb), while histone deacetylase 1 (HDAC1) and HDAC2 enzymatically remove Kbhb. We demonstrate that p300-dependent histone Kbhb can directly mediate in vitro transcription. Moreover, a comprehensive analysis of Kbhb substrates in mammalian cells has identified 3248 Kbhb sites on 1397 substrate proteins. The dependence of histone Kbhb on p300 argues that enzyme-catalyzed acylation is the major mechanism for nuclear Kbhb. Our study thus reveals key regulatory elements for the Kbhb pathway, laying a foundation for studying its roles in diverse cellular processes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Jiang, H.; Dempsey, D. R.; Cole, P. A.
Ubiquitin Ligase Activities of WWP1 Germline Variants K740N and N745S Journal Article
In: Biochemistry, 2021, ISSN: 1520-4995.
Abstract | Links | BibTeX | Tags:
@article{1573454,
title = {Ubiquitin Ligase Activities of WWP1 Germline Variants K740N and N745S},
author = {H. Jiang and D. R. Dempsey and P. A. Cole},
doi = {10.1021/acs.biochem.0c00869},
issn = {1520-4995},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Biochemistry},
abstract = {WWP1 is an E3 ubiquitin ligase that has been reported to target the tumor suppressor lipid phosphatase PTEN. K740N and N745S are recently identified germline variants of WWP1 that have been linked to PTEN-associated cancers [Lee, Y. R., et al. (2020) ]. These WWP1 variants have been suggested to release WWP1 from its native autoinhibited state, thereby promoting enhanced PTEN ubiquitination as a mechanism for driving cancer. Using purified proteins and enzymatic assays, we investigate the possibility that K740N and N745S WWP1 possess enhanced ubiquitin ligase activity and demonstrate that these variants are similar to the wild type (WT) in both autoubiquitination and PTEN ubiquitination. Furthermore, K740N and N745S WWP1 show dependencies similar to those of WT in terms of allosteric activation by an engineered ubiquitin variant, upstream E2 concentration, and substrate ubiquitin concentration. Transfected WWP1 WT and mutants demonstrate comparable effects on cellular PTEN levels. These findings challenge the idea that K740N and N745S WWP1 variants promote cancer by enhanced PTEN ubiquitination.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Jiang, H.; Cole, P. A.
In: Curr. Protoc. Mol. Bio., pp. e14, 2021, ISSN: 2691-1299.
Abstract | Links | BibTeX | Tags:
@article{1573455,
title = {N-Terminal Protein Labeling with N-Hydroxysuccinimide Esters and Microscale Thermophoresis Measurements of Protein-Protein Interactions Using Labeled Protein},
author = {H. Jiang and P. A. Cole},
doi = {10.1002/cpz1.14},
issn = {2691-1299},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Curr. Protoc. Mol. Bio.},
pages = {e14},
abstract = {Protein labeling strategies have been explored for decades to study protein structure, function, and regulation. Fluorescent labeling of a protein enables the study of protein-protein interactions through biophysical methods such as microscale thermophoresis (MST). MST measures the directed motion of a fluorescently labeled protein in response to microscopic temperature gradients, and the protein’s thermal mobility can be used to determine binding affinity. However, the stoichiometry and site specificity of fluorescent labeling are hard to control, and heterogeneous labeling can generate inaccuracies in binding measurements. Here, we describe an easy-to-apply protocol for high-stoichiometric, site-specific labeling of a protein at its N-terminus with N-hydroxysuccinimide (NHS) esters as a means to measure protein-protein interaction affinity by MST. This protocol includes guidelines for NHS ester labeling, fluorescent-labeled protein purification, and MST measurement using a labeled protein. As an example of the entire workflow, we additionally provide a protocol for labeling a ubiquitin E3 enzyme and testing ubiquitin E2-E3 enzyme binding affinity. These methods are highly adaptable and can be extended for protein interaction studies in various biological and biochemical circumstances. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Labeling a protein of interest at its N-terminus with NHS esters through stepwise reaction Alternate Protocol: Labeling a protein of interest at its N-terminus with NHS esters through a one-pot reaction Basic Protocol 2: Purifying the N-terminal fluorescent-labeled protein and determining its concentration and labeling efficiency Basic Protocol 3: Using MST to determine the binding affinity of an N-terminal fluorescent-labeled protein to a binding partner. Basic Protocol 4: NHS ester labeling of ubiquitin E3 ligase WWP2 and measurement of the binding affinity between WWP2 and an E2 conjugating enzyme by the MST binding assay.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Na, M.; Martin, G. M.; Karl, D. L.; Sun, J.; Torres-Martin, M.; Itonaga, H.; Martinez, C.; Chen, S.; Xu, Y.; Duffort, S.; Hamard, P. -J.; Chen, C.; Cimmino, L.; Yang, F. -C.; Zucconi, B.; Cole, P. A.; Xu, M.; Figueroa, M. E.; Nimer, S. D.
P300 Suppresses the Transition of Myelodysplastic Syndrome to Acute Myeloid Leukemia Journal Article
In: JCI Insights, vol. 6, pp. e138478, 2021.
BibTeX | Tags:
@article{1624370,
title = {P300 Suppresses the Transition of Myelodysplastic Syndrome to Acute Myeloid Leukemia},
author = {M. Na and G. M. Martin and D. L. Karl and J. Sun and M. Torres-Martin and H. Itonaga and C. Martinez and S. Chen and Y. Xu and S. Duffort and P. -J. Hamard and C. Chen and L. Cimmino and F. -C. Yang and B. Zucconi and P. A. Cole and M. Xu and M. E. Figueroa and S. D. Nimer},
year = {2021},
date = {2021-01-01},
journal = {JCI Insights},
volume = {6},
pages = {e138478},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pujari, S. S; Wu, M.; Thomforde, J.; Wang, Z. A.; Chao, C.; Olson, N.; Erber, L.; Pomerantz, W.; Cole, P. A.; Tretyakova, N.
Site-specific 5-Formyl Cytosine Mediated DNA-Histone Crosslinks: Synthesis and Polymerase Bypass by Human DNA Polymerase η Journal Article
In: Angew. Chem. Int. Ed., vol. 60, pp. 26489-26494, 2021.
BibTeX | Tags:
@article{1624375,
title = {Site-specific 5-Formyl Cytosine Mediated DNA-Histone Crosslinks: Synthesis and Polymerase Bypass by Human DNA Polymerase η},
author = {S. S Pujari and M. Wu and J. Thomforde and Z. A. Wang and C. Chao and N. Olson and L. Erber and W. Pomerantz and P. A. Cole and N. Tretyakova},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Angew. Chem. Int. Ed.},
volume = {60},
pages = {26489-26494},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2020
Hsu, J. W.; Bai, M.; Li, K.; Yang, J. S.; Chu, N.; Cole, P. A.; Eck, M. J.; Li, J.; Hsu, V. W.
The protein kinase Akt acts as a coat adaptor in endocytic recycling Journal Article
In: Nat. Cell Biol., vol. 22, no. 8, pp. 927–933, 2020.
@article{pmid32541877,
title = {The protein kinase Akt acts as a coat adaptor in endocytic recycling},
author = {J. W. Hsu and M. Bai and K. Li and J. S. Yang and N. Chu and P. A. Cole and M. J. Eck and J. Li and V. W. Hsu},
year = {2020},
date = {2020-08-01},
journal = {Nat. Cell Biol.},
volume = {22},
number = {8},
pages = {927–933},
abstract = {Coat proteins have a central role in vesicular transport by binding to cargoes for their sorting into intracellular pathways. Cargo recognition is mediated by components of the coat complex known as adaptor proteins1-3. We previously showed that Arf-GAP with coil-coil, ANK repeat and PH domain-containing protein 1 (ACAP1) functions as an adaptor for a clathrin coat complex that has a function in endocytic recycling4-6. Here, we show that the protein kinase Akt acts as a co-adaptor in this complex, and is needed in conjunction with ACAP1 to bind to cargo proteins to promote their recycling. In addition to advancing the understanding of endocytic recycling, we uncover a fundamentally different function in which a kinase acts, as Akt in this case is an effector rather than a regulator in a cellular event.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chu, N.; Viennet, T.; Bae, H.; Salguero, A.; Boeszoermenyi, A.; Arthanari, H.; Cole, P. A.
The Structural Determinants of PH Domain-Mediated Regulation of Akt Revealed by Segmental Labeling Journal Article
In: Elife, vol. 9, 2020.
@article{pmid32744507,
title = {The Structural Determinants of PH Domain-Mediated Regulation of Akt Revealed by Segmental Labeling},
author = {N. Chu and T. Viennet and H. Bae and A. Salguero and A. Boeszoermenyi and H. Arthanari and P. A. Cole},
year = {2020},
date = {2020-08-01},
journal = {Elife},
volume = {9},
abstract = {Akt is a critical protein kinase that governs cancer cell growth and metabolism. Akt appears to be autoinhibited by an intramolecular interaction between its N-terminal pleckstrin homology (PH) domain and kinase domain, which is relieved by C-tail phosphorylation, but the precise molecular mechanisms remain elusive. Here we use a combination of protein semisynthesis, NMR, and enzymological analysis to characterize structural features of the PH domain in its autoinhibited and activated states. We find that Akt autoinhibition depends on the length/flexibility of the PH-kinase linker. We identify a role for a dynamic short segment in the PH domain that appears to regulate autoinhibition and PDK1-catalyzed phosphorylation of Thr308 in the activation loop. We determine that Akt allosteric inhibitor MK2206 drives distinct PH domain structural changes compared to baseline autoinhibited Akt. These results highlight how the conformational plasticity of Akt governs the delicate control of its catalytic properties.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Wang, Z. A.; Cole, P. A.
The Chemical Biology of Reversible Lysine Post-translational Modifications Journal Article
In: Cell Chem. Biol., 2020.
@article{pmid32698016,
title = {The Chemical Biology of Reversible Lysine Post-translational Modifications},
author = {Z. A. Wang and P. A. Cole},
year = {2020},
date = {2020-07-01},
urldate = {2020-07-01},
journal = {Cell Chem. Biol.},
abstract = {Lysine (Lys) residues in proteins undergo a wide range of reversible post-translational modifications (PTMs), which can regulate enzyme activities, chromatin structure, protein-protein interactions, protein stability, and cellular localization. Here we discuss the "writers," ërasers," and "readers" of some of the common protein Lys PTMs and summarize examples of their major biological impacts. We also review chemical biology approaches, from small-molecule probes to protein chemistry technologies, that have helped to delineate Lys PTM functions and show promise for a diverse set of biomedical applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Morrison-Smith, C. D.; Knox, T. M.; Filic, I.; Soroko, K. M.; Eschle, B. K.; Wilkens, M. K.; Gokhale, P. C.; Giles, F.; Griffin, A.; Brown, B.; Shapiro, G. I.; Zucconi, B. E.; Cole, P. A.; Lemieux, M. E.; French, C. A.
Combined Targeting of the BRD4-NUT-p300 Axis in NUT Midline Carcinoma by Dual Selective Bromodomain Inhibitor, NEO2734 Journal Article
In: Mol. Cancer Ther., vol. 19, no. 7, pp. 1406–1414, 2020.
@article{pmid32371576,
title = {Combined Targeting of the BRD4-NUT-p300 Axis in NUT Midline Carcinoma by Dual Selective Bromodomain Inhibitor, NEO2734},
author = {C. D. Morrison-Smith and T. M. Knox and I. Filic and K. M. Soroko and B. K. Eschle and M. K. Wilkens and P. C. Gokhale and F. Giles and A. Griffin and B. Brown and G. I. Shapiro and B. E. Zucconi and P. A. Cole and M. E. Lemieux and C. A. French},
year = {2020},
date = {2020-07-01},
journal = {Mol. Cancer Ther.},
volume = {19},
number = {7},
pages = {1406–1414},
abstract = {NUT midline carcinoma (NMC) is a rare, aggressive subtype of squamous carcinoma that is driven by the BRD4-NUT fusion oncoprotein. BRD4, a BET protein, binds to chromatin through its two bromodomains, and NUT recruits the p300 histone acetyltransferse (HAT) to activate transcription of oncogenic target genes. BET-selective bromodomain inhibitors have demonstrated on-target activity in patients with NMC, but with limited efficacy. P300, like BRD4, contains a bromodomain. We show that combining selective p300/CBP and BET bromodomain inhibitors, GNE-781 and OTX015, respectively, induces cooperative depletion of MYC and synergistic inhibition of NMC growth. Treatment of NMC cells with the novel dual p300/CBP and BET bromodomain-selective inhibitor, NEO2734, potently inhibits growth and induces differentiation of NMC cells in vitro; findings that correspond with potentiated transcriptional effects from combined BET and p300 bromodomain inhibition. In three disseminated NMC xenograft models, NEO2734 provided greater growth inhibition, with tumor regression and significant survival benefit seen in two of three models, compared with a lead clinical BET inhibitor or "standard" chemotherapy. Our findings provide a strong rationale for clinical study of NEO2734 in patients with NMC. Moreover, the synergistic inhibition of NMC growth by CBP/p300 and BET bromodomain inhibition lays the groundwork for greater mechanistic understanding of the interplay between p300 and BRD4-NUT that drives this cancer.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Wang, Z. A.; Millard, C. J.; Lin, C. L.; Gurnett, J. E.; Wu, M.; Lee, K.; Fairall, L.; Schwabe, J. W.; Cole, P. A.
Diverse nucleosome Site-Selectivity among histone deacetylase complexes Journal Article
In: Elife, vol. 9, 2020.
@article{pmid32501215,
title = {Diverse nucleosome Site-Selectivity among histone deacetylase complexes},
author = {Z. A. Wang and C. J. Millard and C. L. Lin and J. E. Gurnett and M. Wu and K. Lee and L. Fairall and J. W. Schwabe and P. A. Cole},
year = {2020},
date = {2020-06-01},
journal = {Elife},
volume = {9},
abstract = {Histone acetylation regulates chromatin structure and gene expression and is removed by histone deacetylases (HDACs). HDACs are commonly found in various protein complexes to confer distinct cellular functions, but how the multi-subunit complexes influence deacetylase activities and site-selectivities in chromatin is poorly understood. Previously we reported the results of studies on the HDAC1 containing CoREST complex and acetylated nucleosome substrates which revealed a notable preference for deacetylation of histone H3 acetyl-Lys9 vs. acetyl-Lys14 (Wu et al, 2018). Here we analyze the enzymatic properties of five class I HDAC complexes: CoREST, NuRD, Sin3B, MiDAC and SMRT with site-specific acetylated nucleosome substrates. Our results demonstrate that these HDAC complexes show a wide variety of deacetylase rates in a site-selective manner. A Gly13 in the histone H3 tail is responsible for a sharp reduction in deacetylase activity of the CoREST complex for H3K14ac. These studies provide a framework for connecting enzymatic and biological functions of specific HDAC complexes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cole, P. A.; Shapiro, T.
Paul Talalay 1923-2019 A Biographical Memoir Journal Article
In: National Academy of Sciences, 2020.
@article{1573452,
title = {Paul Talalay 1923-2019 A Biographical Memoir},
author = {P. A. Cole and T. Shapiro},
url = {http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/talalay-paul.pdf},
year = {2020},
date = {2020-01-01},
journal = {National Academy of Sciences},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Jiang, H.; D’Agostino, G. D.; Cole, P. A.; Dempsey, D. R.
Selective protein N-terminal labeling with N-hydroxysuccinimide esters Journal Article
In: Methods Enzymol., vol. 639, pp. 333–353, 2020.
@article{pmid32475408,
title = {Selective protein N-terminal labeling with N-hydroxysuccinimide esters},
author = {H. Jiang and G. D. D’Agostino and P. A. Cole and D. R. Dempsey},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Methods Enzymol.},
volume = {639},
pages = {333–353},
abstract = {In order to gain detailed insight into the biochemical behavior of proteins, researchers have developed chemical tools to incorporate new functionality into proteins beyond the canonical 20 amino acids. Important considerations regarding effective chemical modification of proteins include chemoselectivity, near stoichiometric labeling, and reaction conditions that maintain protein stability. Taking these factors into account, we discuss an N-terminal labeling strategy that employs a simple two-step öne-pot" method using N-hydroxysuccinimide (NHS) esters. The first step converts a R-NHS ester into a more chemoselective R-thioester. The second step reacts the in situ generated R-thioester with a protein that harbors an N-terminal cysteine to generate a new amide bond. This labeling reaction is selective for the N-terminus with high stoichiometry. Herein, we provide a detailed description of this method and further highlight its utility with a large protein (>100kDa) and labeling with a commonly used cyanine dye.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mattevi, A.; Cole, P. A.
Editorial Overview: Biological catalysis at the cross-roads of signaling and metabolism Journal Article
In: Curr. Opin. Struct. Biol., vol. 59, pp. iii-iv, 2020.
BibTeX | Tags:
@article{1523679,
title = {Editorial Overview: Biological catalysis at the cross-roads of signaling and metabolism},
author = {A. Mattevi and P. A. Cole},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Curr. Opin. Struct. Biol.},
volume = {59},
pages = {iii-iv},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Xiong, Y.; Wang, L.; Giorgio, E. D.; Akimova, T.; Beier, U. H.; Han, R.; Trevisanut, M.; Kalin, J. H.; Cole, P. A.; Hancock, W. W.
Essential Role of the CoREST Complex in Foxp3+ T-Regulatory Cell Functions Journal Article
In: J. Clin. Invest., vol. 130, pp. 1830-1842, 2020.
BibTeX | Tags:
@article{1523678,
title = {Essential Role of the CoREST Complex in Foxp3+ T-Regulatory Cell Functions},
author = {Y. Xiong and L. Wang and E. D. Giorgio and T. Akimova and U. H. Beier and R. Han and M. Trevisanut and J. H. Kalin and P. A. Cole and W. W. Hancock},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {J. Clin. Invest.},
volume = {130},
pages = {1830-1842},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Song, Y.; Dagil, L.; Fairall, L.; Robertson, N.; Wu, M.; Ragan, T. J.; Savva, C. G.; Saleh, A.; Morone, N.; Kunze, M. B. A.; Jamieson, A. G.; Cole, P. A.; Hansen, D. F.; Schwabe, J. W. R.
Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex Journal Article
In: Cell Rep., vol. 30, pp. 2699-2711, 2020.
BibTeX | Tags:
@article{1523677,
title = {Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex},
author = {Y. Song and L. Dagil and L. Fairall and N. Robertson and M. Wu and T. J. Ragan and C. G. Savva and A. Saleh and N. Morone and M. B. A. Kunze and A. G. Jamieson and P. A. Cole and D. F. Hansen and J. W. R. Schwabe},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Cell Rep.},
volume = {30},
pages = {2699-2711},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Miller, S. A.; Policastro, R. A.; Savant, S. S.; Sriramkumar, S.; Ding, N.; Lu, X.; Mohammad, H. P.; Cao, S.; Kalin, J. H.; Cole, P. A.; Zentner, G. E.; O’Hagan, H. M.
Lysine-Specific Demethylase 1 Mediates AKT Activity and Promotes Epithelial-to-Mesenchymal Transition in PIK3CA-Mutant Colorectal Cancer Journal Article
In: Mol. Cancer Res., vol. 18, no. 2, pp. 264–277, 2020.
@article{pmid31704733,
title = {Lysine-Specific Demethylase 1 Mediates AKT Activity and Promotes Epithelial-to-Mesenchymal Transition in PIK3CA-Mutant Colorectal Cancer},
author = {S. A. Miller and R. A. Policastro and S. S. Savant and S. Sriramkumar and N. Ding and X. Lu and H. P. Mohammad and S. Cao and J. H. Kalin and P. A. Cole and G. E. Zentner and H. M. O’Hagan},
year = {2020},
date = {2020-01-01},
journal = {Mol. Cancer Res.},
volume = {18},
number = {2},
pages = {264–277},
abstract = {Activation of the epithelial-to-mesenchymal transition (EMT) program is a critical mechanism for initiating cancer progression and migration. Colorectal cancers contain many genetic and epigenetic alterations that can contribute to EMT. Mutations activating the PI3K/AKT signaling pathway are observed in >40% of patients with colorectal cancer contributing to increased invasion and metastasis. Little is known about how oncogenic signaling pathways such as PI3K/AKT synergize with chromatin modifiers to activate the EMT program. Lysine-specific demethylase 1 (LSD1) is a chromatin-modifying enzyme that is overexpressed in colorectal cancer and enhances cell migration. In this study, we determine that LSD1 expression is significantly elevated in patients with colorectal cancer with mutation of the catalytic subunit of PI3K, PIK3CA, compared with patients with colorectal cancer with WT PIK3CA. LSD1 enhances activation of the AKT kinase in colorectal cancer cells through a noncatalytic mechanism, acting as a scaffolding protein for the transcription-repressing CoREST complex. In addition, growth of PIK3CA-mutant colorectal cancer cells is uniquely dependent on LSD1. Knockdown or CRISPR knockout of LSD1 blocks AKT-mediated stabilization of the EMT-promoting transcription factor Snail and effectively blocks AKT-mediated EMT and migration. Overall, we uniquely demonstrate that LSD1 mediates AKT activation in response to growth factors and oxidative stress, and LSD1-regulated AKT activity promotes EMT-like characteristics in a subset of PIK3CA-mutant cells. IMPLICATIONS: Our data support the hypothesis that inhibitors targeting the CoREST complex may be clinically effective in patients with colorectal cancer harboring PIK3CA mutations.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Wang, Z. A.; Cole, P. A.
Methods and Applications of Expressed Protein Ligation Journal Article
In: Methods Mol. Biol., vol. 2133, pp. 1–13, 2020.
@article{pmid32144660,
title = {Methods and Applications of Expressed Protein Ligation},
author = {Z. A. Wang and P. A. Cole},
year = {2020},
date = {2020-01-01},
journal = {Methods Mol. Biol.},
volume = {2133},
pages = {1–13},
abstract = {Expressed protein ligation is a method of protein semisynthesis and typically involves the reaction of recombinant protein C-terminal thioesters with N-cysteine containing synthetic peptides in a chemoselective ligation. The recombinant protein C-terminal thioesters are produced by exploiting the action of nature’s inteins which are protein modules that catalyze protein splicing. This chapter discusses the basic principles of expressed protein ligation and recent advances and applications in this protein semisynthesis field. Comparative strengths and weaknesses of the method and future challenges are highlighted.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}