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Asymmetric Engagement of Dimeric CRL3 KBTBD4 by the Molecular Glue UM171 Licenses Degradation of HDAC1/2 Complexes.
Yeo MJ, Zhang O, Xie X, Nam E, Payne NC, Gosavi PM, Kwok HS, Iram I, Lee C, Li J, Chen NJ, Jiang H, Wang ZA, Lee K, Mao H, Harry SA, Barakat IA, Takahashi M, Waterbury AL, Barone M, Mattevi A, Bar-Peled L, Cole PA, Mazitschek R, Liau BB, Zheng N. Yeo MJ, et al. bioRxiv [Preprint]. 2024 May 14:2024.05.14.593897. doi: 10.1101/2024.05.14.593897. bioRxiv. 2024. PMID: 38798619 Free PMC article. Preprint.
UM171 glues asymmetric CRL3-HDAC1/2 assembly to degrade CoREST corepressors.
Yeo MJR, Zhang O, Xie X, Nam E, Payne NC, Gosavi PM, Kwok HS, Iram I, Lee C, Li J, Chen NJ, Nguyen K, Jiang H, Wang ZA, Lee K, Mao H, Harry SA, Barakat IA, Takahashi M, Waterbury AL, Barone M, Mattevi A, Carr SA, Udeshi ND, Bar-Peled L, Cole PA, Mazitschek R, Liau BB, Zheng N. Yeo MJR, et al. Nature. 2025 Mar;639(8053):232-240. doi: 10.1038/s41586-024-08532-4. Epub 2025 Feb 12. Nature. 2025. PMID: 39939761 Free PMC article.
KBTBD4 Cancer Hotspot Mutations Drive Neomorphic Degradation of HDAC1/2 Corepressor Complexes.
Xie X, Zhang O, Yeo MJR, Lee C, Harry SA, Paul L, Li Y, Payne NC, Nam E, Kwok HS, Jiang H, Mao H, Hadley JL, Lin H, Batts M, Gosavi PM, D'Angiolella V, Cole PA, Mazitschek R, Northcott PA, Zheng N, Liau BB. Xie X, et al. bioRxiv [Preprint]. 2024 May 14:2024.05.14.593970. doi: 10.1101/2024.05.14.593970. bioRxiv. 2024. PMID: 38798357 Free PMC article. Preprint.
An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing.
Waterbury AL, Kwok HS, Lee C, Narducci DN, Freedy AM, Su C, Raval S, Reiter AH, Hawkins W, Lee K, Li J, Hoenig SM, Vinyard ME, Cole PA, Hansen AS, Carr SA, Papanastasiou M, Liau BB. Waterbury AL, et al. Mol Cell. 2024 Jun 20;84(12):2238-2254.e11. doi: 10.1016/j.molcel.2024.05.017. Epub 2024 Jun 12. Mol Cell. 2024. PMID: 38870936 Free PMC article.
Converging mechanism of UM171 and KBTBD4 neomorphic cancer mutations.
Xie X, Zhang O, Yeo MJR, Lee C, Tao R, Harry SA, Payne NC, Nam E, Paul L, Li Y, Kwok HS, Jiang H, Mao H, Hadley JL, Lin H, Batts M, Gosavi PM, D'Angiolella V, Cole PA, Mazitschek R, Northcott PA, Zheng N, Liau BB. Xie X, et al. Nature. 2025 Mar;639(8053):241-249. doi: 10.1038/s41586-024-08533-3. Epub 2025 Feb 12. Nature. 2025. PMID: 39939763 Free PMC article.