BAP1

BAP1 Full Name

BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)

BAP1 Introduction

BRCA1 Associated Protein 1 (BAP1) is a highly conserved nuclear deubiquitinase and tumor suppressor protein that plays indispensable roles in regulating genomic stability, epigenetic modification, and cellular homeostasis in human tissues. Encoded by the BAP1 gene located on human chromosome 3p21.31, this enzyme belongs to the ubiquitin-specific protease (USP) family and functions as a critical modulator of protein ubiquitination, a core post-translational modification governing protein stability, localization, and signaling activity. BAP1 is ubiquitously expressed in normal human tissues, with prominent functional activity in proliferative cells, epithelial tissues, and immune cells. Unlike ordinary deubiquitinases, BAP1 acts as a multifunctional scaffold protein that coordinates with multiple nuclear complexes to regulate DNA damage repair, cell cycle checkpoint control, chromatin remodeling, and apoptotic signaling pathways. A large body of biomedical research has confirmed that loss-of-function mutations, downregulated expression, or functional inactivation of BAP1 are closely associated with tumor susceptibility, malignant progression, and inflammatory disorders, making BAP1 a core tumor suppressor gene and a high-value clinical biomarker for disease diagnosis and targeted therapy.

Figure 1. The roles of BAP1 in genome stability and tumor suppression.(Kwon J, Lee D, Lee S A. 2023)

Core Physiological Functions of BAP1
BAP1 exerts diverse essential physiological functions centered on genome protection and cellular homeostasis maintenance in normal human cells. Primarily, BAP1 is a key regulator of DNA double-strand break repair, which stabilizes core DNA repair proteins by deubiquitination, promoting accurate homologous recombination repair and preventing irreversible genomic mutation and chromosomal aberration. In cell cycle regulation, BAP1 modulates the activity of cell cycle checkpoint proteins, inhibiting abnormal cell cycle overactivation and blocking uncontrolled cell proliferation to maintain normal cell growth rhythm. BAP1 also participates in epigenetic regulation by stabilizing polycomb repressive complexes, controlling the expression of developmental and cell differentiation-related genes to support normal tissue development and cell fate determination. Furthermore, BAP1 regulates cellular senescence and immune homeostasis, suppressing chronic inflammatory activation and maintaining the normal physiological state of epithelial and mesenchymal tissues across multiple organ systems.

Pathophysiological and Clinical Significance of BAP1
Genetic mutation, epigenetic silencing, or functional deficiency of BAP1 is strongly linked to tumorigenesis, hereditary cancer syndromes, and multiple human diseases with high clinical relevance. Germline BAP1 mutations cause BAP1 tumor predisposition syndrome (BAP1-TPDS), an autosomal dominant hereditary disorder that significantly increases the risk of developing multiple malignant tumors, including uveal melanoma, cutaneous melanoma, malignant mesothelioma, renal cell carcinoma, and hepatocellular carcinoma. Somatic BAP1 inactivation is extremely common in sporadic malignant tumors, driving tumor proliferation, metastasis, and drug resistance by inducing genomic instability, dysregulating cell cycle checkpoints, and remodeling the tumor microenvironment. In non-tumor diseases, BAP1 dysfunction contributes to chronic inflammatory tissue injury and fibrotic lesion formation by disrupting immune homeostasis and DNA repair capacity. Clinically, BAP1 mutation status and protein expression levels serve as critical prognostic indicators for tumor malignancy, recurrence risk, and patient survival, representing a promising therapeutic target for precision cancer treatment and disease intervention.

Alternate Names for BAP1

BAP1; BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase); ubiquitin carboxyl-terminal hydrolase BAP1; hucep 6; KIAA0272; UCHL2; cerebral protein 6; cerebral protein-13; TPDS; hucep-6; HUCEP-13; FLJ35406; FLJ37180; DKFZp686N04275;

• 1.Kwon J, Lee D, Lee S A. BAP1 as a guardian of genome stability: implications in human cancer. Experimental & Molecular Medicine, 2023, 55(4): 745-754.