BRCA1-associated protein-1 (BAP1)

BRCA1-associated protein-1 (BAP1) is a deubiquitinating enzyme (DUB) belonging to the ubiquitin C-terminal hydrolase family that plays a critical role in chromatin remodeling and DNA damage response [1, 2]. It functions primarily by removing ubiquitin from histone H2A and other proteins, thereby regulating gene expression and maintaining genomic stability [1]. BAP1 acts as a potent tumor suppressor, and its loss-of-function mutations are strongly associated with a variety of malignancies, including malignant mesothelioma, uveal melanoma, and clear cell renal cell carcinoma [2, 3]. In the context of drug development, BAP1 is a key target for synthetic lethality strategies; for instance, BAP1-deficient tumors show heightened sensitivity to EZH2 inhibitors like tazemetostat [4, 5]. Additionally, its role in homologous recombination repair makes BAP1-mutant cancers potential candidates for PARP inhibitor therapy [6]. Understanding BAP1 status is essential for patient stratification in clinical trials targeting epigenetic regulators and DNA repair pathways [5].

Other names

Ubiquitin carboxyl-terminal hydrolase BAP1UCHL2HUCEP-13Cerebral protein 6

BAP1 functions as a deubiquitinating enzyme that regulates the Polycomb repressive complex and DNA repair; therapeutic strategies involve synthetic lethality where EZH2 inhibitors or PARP inhibitors are used to exploit the vulnerabilities created by BAP1 loss [4, 6].