BAP1 as a guardian of genome stability: implications in human cancer
Abstract 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 id...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-023-00979-1 |
| _version_ | 1797827634130845696 |
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| author | Jongbum Kwon Daye Lee Shin-Ai Lee |
| author_facet | Jongbum Kwon Daye Lee Shin-Ai Lee |
| author_sort | Jongbum Kwon |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T12:51:29Z |
| format | Article |
| id | doaj.art-4018f2b991624efa9fda82f2467aad08 |
| institution | Directory Open Access Journal |
| issn | 2092-6413 |
| language | English |
| last_indexed | 2024-04-09T12:51:29Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj.art-4018f2b991624efa9fda82f2467aad082023-05-14T11:09:48ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132023-04-0155474575410.1038/s12276-023-00979-1BAP1 as a guardian of genome stability: implications in human cancerJongbum Kwon0Daye Lee1Shin-Ai Lee2Department of Life Science, Ewha Womans UniversityDepartment of Life Science, Ewha Womans UniversityDepartment of Life Science, Ewha Womans UniversityAbstract 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.https://doi.org/10.1038/s12276-023-00979-1 |
| spellingShingle | Jongbum Kwon Daye Lee Shin-Ai Lee BAP1 as a guardian of genome stability: implications in human cancer Experimental and Molecular Medicine |
| title | BAP1 as a guardian of genome stability: implications in human cancer |
| title_full | BAP1 as a guardian of genome stability: implications in human cancer |
| title_fullStr | BAP1 as a guardian of genome stability: implications in human cancer |
| title_full_unstemmed | BAP1 as a guardian of genome stability: implications in human cancer |
| title_short | BAP1 as a guardian of genome stability: implications in human cancer |
| title_sort | bap1 as a guardian of genome stability implications in human cancer |
| url | https://doi.org/10.1038/s12276-023-00979-1 |
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