| Autor: |
Kah-Leong Lim, Monica Schenone, Jacqueline S. Garcia, Eunice S. Wang, Yingtian Xie, Henry W. Long, Eric S. Winer, Vivian J. Bardwell, R. C. Lindsley, Lukasz P. Gondek, Eva Johanna Schaefer, Marlise R. Luskin, Clifford A. Meyer, Richard Stone, Rahul S. Vedula, Annie Apffel, Martin Carroll, Emmalee R. Adelman, Murdock Hm, Steven A. Carr, Paloma Cejas, Iman Fares, Mario Figueroa, Huan Wang, Christopher J. Gibson, Gearhart |
| Rok vydání: |
2021 |
| Předmět: |
|
| Popis: |
SummaryBCOR and its paralog BCORL1 encode subunits of the Polycomb repressive complex 1.1 (PRC1.1) and are recurrently mutated in myeloid malignancies. We show that leukemia-associated BCOR/BCORL1 mutations unlink the PRC1.1 RING-PCGF enzymatic core from the KDM2B-containing chromatin targeting auxiliary subcomplex, either by causing complete protein loss or expression of a C-terminally truncated protein lacking the PCGF Ub-like fold discriminator (PUFD) domain. By uncoupling PRC1.1 repressive function from target genes, BCOR/BCORL1 mutations activate aberrant cell signaling programs that confer acquired resistance to treatment. This study provides a mechanistic basis for Polycomb repressive dysfunction as a key oncogenic driver in myeloid malignancies and identifies a potential strategy for targeted therapy in BCOR-mutated cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
