BRCA1-associated protein 1 (BAP1) (BAP1)

BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme (DUB) belonging to the ubiquitin carboxy-terminal hydrolase (UCH) family that acts as a critical tumor suppressor (UniProt Q92560). It functions primarily by removing monoubiquitin from histone H2A as part of the Polycomb repressive deubiquitinase (PR-DUB) complex, thereby regulating chromatin structure and gene expression (PubMed: 20436459). Beyond epigenetic regulation, BAP1 is involved in DNA damage repair, cell cycle control, and programmed cell death (PubMed: 22203037). Germline or somatic loss-of-function mutations in the BAP1 gene are linked to BAP1 tumor predisposition syndrome, which significantly increases the risk of developing malignant mesothelioma, uveal melanoma, and clear cell renal cell carcinoma (PubMed: 21822264). While BAP1 itself is not typically targeted by inhibitory drugs due to its tumor-suppressive role, its absence creates therapeutic vulnerabilities. For instance, BAP1-deficient tumors show sensitivity to EZH2 inhibitors like Tazemetostat and PARP inhibitors like Olaparib through synthetic lethality (ClinicalTrials.gov: NCT02860286). Consequently, BAP1 status serves as a vital biomarker for patient stratification in clinical trials exploring these targeted therapies.

Other names

UCHL2Cerebral protein 6hu-Li 3Ubiquitin carboxyl-terminal hydrolase BAP1

Synthetic lethality through EZH2 or PARP inhibition in BAP1-deficient cells