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BAP1 as a guardian of genome stability: implications in human cancer
BAP1 is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase with a wide array of biological activities. Studies in which advanced sequencing technologies were used have uncovered a link between BAP1 and human cancer. Somatic and germline mutations of the BAP1 gene have been identified...
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Published in: | Experimental & molecular medicine 2023, 55(0), , pp.745-754 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | BAP1 is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase with a wide array of biological activities. Studies in which advanced sequencing technologies were used have uncovered a link between BAP1 and human cancer. Somatic and germline mutations of the
BAP1
gene have been identified in multiple human cancers, with a particularly high frequency in mesothelioma, uveal melanoma and clear cell renal cell carcinoma. BAP1 cancer syndrome highlights that all carriers of inherited
BAP1
-inactivating mutations develop at least one and often multiple cancers with high penetrance during their lifetime. These findings, together with substantial evidence indicating the involvement of BAP1 in many cancer-related biological activities, strongly suggest that BAP1 functions as a tumor suppressor. Nonetheless, the mechanisms that account for the tumor suppressor function of BAP1 have only begun to be elucidated. Recently, the roles of BAP1 in genome stability and apoptosis have drawn considerable attention, and they are compelling candidates for key mechanistic factors. In this review, we focus on genome stability and summarize the details of the cellular and molecular functions of BAP1 in DNA repair and replication, which are crucial for genome integrity, and discuss the implications for BAP1-associated cancer and relevant therapeutic strategies. We also highlight some unresolved issues and potential future research directions.
Cancer: Investigating a genome-guarding protein
A protein called BAP1, which removes tags marking proteins for degradation, is an important guardian of genome stability, and understanding its function may help in developing cancer therapies. People with mutations that inactivate BAP1 function always develop at least one and often multiple cancers, but specifically how BAP1 mutations cause cancer is not well understood. Jongbum Kwon and co-workers at Ewha Womans University in Seoul, South Korea, have reviewed how BAP1 functions, focusing on DNA repair. The authors report that BAP1 is crucial for repair of large DNA lesions, such as those caused by UV damage, and plays key roles in DNA replication, chromosome segregation, and disposal of cells with damaged DNA. These activities make BAP1 a powerful tumor suppressor, and improving our understanding of its mechanisms could point the way to new cancer treatments. |
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ISSN: | 2092-6413 1226-3613 2092-6413 |
DOI: | 10.1038/s12276-023-00979-1 |