Dr. El Bachir Affar
Associate Professor, Department of Biochemistry and Molecular Medicine, Université de Montréal
PI: Prof. Ho-Sung Rhee
12 to 1 PM
IB 140 & Zoom
Title
The Multi‑layered regulation of the deubiquitinase BAP1: from nuclear entry to chromatin‑driven transcription
Abstract
BAP1 is a tumor‑suppressor deubiquitinase whose activity and genomic targeting are tightly coordinated by its interacting partners. UBE2O ubiquitinates the nuclear localization signal, thus retaining BAP1 in the cytoplasm. Proper BAP1 folding and its own catalytic activity can reverse this modification, restoring nuclear entry and function. In the nucleus, BAP1 binds ASXL1/2/3 via their DEUBAD domains to assemble the PR‑DUB complex. ASXL binding creates a composite ubiquitin-binding interface that stimulates BAP1 activity toward H2A‑K119ub within nucleosomes, thereby counteracting PRC1‑mediated transcriptional repression. Moreover, FOXK1/2, Forkhead transcription factors, interact with BAP1‑ASXL complexes to recruit them to specific chromatin sites, coupling local deubiquitination to transcriptional outcomes at cell cycle and cancer‑relevant genes. Together, UBE2O establishes the gate on nuclear access, ASXLs endow catalytic activation and substrate specificity, and FOXK factors ensure recruitment to specific genomic locations, altogether ensuring that the activity and function of BAP1 are both properly localized and productively wired into transcriptional regulation.