[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-376746-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-376746-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","bap1-as-a-guardian-of-genome-stability-implications-in-human-cancer","BAP1 as a guardian of genome stability: implications in human cancer","","BAP1 is a deubiquitinase with diverse biological functions, and advanced sequencing has linked somatic and germline BAP1 alterations to multiple human cancers. High mutation frequency occurs in mesothelioma, uveal melanoma, and clear cell renal cell carcinoma, and inherited BAP1-inactivation defines a cancer syndrome with high penetrance. Evidence supports BAP1 as a tumor suppressor, yet core mechanisms remain partly unresolved. This review emphasizes BAP1 roles in genome stability and apoptosis, particularly DNA repair and replication, and discusses therapeutic implications.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/bap1-as-a-guardian-of-genome-stability-implications-in-human-cancer/376746/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/bap1-as-a-guardian-of-genome-stability-implications-in-human-cancer/376746.png","ImageObject",300,407,{"name":42,"@type":43},"Ezra","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is BAP1 and why is it important for cancer biology?","Question",{"text":63,"@type":64},"BAP1 is a deubiquitinase (deubiquitinase activity-containing protein) with broad biological functions. Somatic and germline BAP1 mutations have been identified across multiple human cancers, supporting a tumor-suppressive role.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which cancers show particularly high BAP1 mutation frequency and what does this imply?",{"text":68,"@type":64},"Mesothelioma, uveal melanoma, and clear cell renal cell carcinoma show particularly high BAP1 mutation frequencies. These findings underpin the concept of BAP1-associated cancer predisposition.",{"name":70,"@type":61,"acceptedAnswer":71},"What does the review focus on regarding BAP1 mechanisms?",{"text":72,"@type":64},"The review highlights BAP1’s roles in genome stability and apoptosis. It summarizes cellular and molecular functions in DNA repair and replication, then discusses implications for BAP1-associated cancer and therapeutic strategies.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},376746,1790469921,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":123,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},1099514068035,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","[www.nature.com/emm](www.nature.com/emm)  \nREVIEW ARTICLE OPEN   \nBAP1 as a guardian of genome stability: implications in human cancer  \nJongbum Kwon1 ✉, Daye Lee 1 and Shin-Ai Lee1,2  \n© The Author(s) 2023  \n|  |  |  |\n| --- | --- | --- |\n|  | 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 |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| some unresolved issues and potential future research directions. |  |  |\n|  | Experimental & Molecular Medicine (2023) 55:745–754; [https://doi.org/10.1038/s12276-023-00979-1](https://doi.org/10.1038/s12276-023-00979-1) |  |\n|  |  |  |\n\nINTRODUCTION  \nBAP1 is a member of the deubiquitinase (DUB) family of proteins and contains a ubiquitin C-terminal hydrolase (UCH) domain1. The BAP1 gene, on chromosome 3p21.3, is deleted or mutated in various human cancer cell lines, and re-expression of BAP1 in H226 mesothelioma cells that initially lacked BAP1 expression reversed their tumorigenicity, suggesting that BAP1 might function as a tumor suppressor1,2. BAP1 carries a nuclear localization signal (NLS) in the C-terminus and functions in both the nucleus and cytoplasm. The ubiquitin-conjugating enzyme UBE2O monoubiquitinates BAP1 at multiple sites in the NLS, thereby inactivating the NLS to induce cytoplasmic sequestration. The DUB activity of BAP1 counteracts NLS ubiquitination, and this auto-deubiquitination enables BAP1 to be transported to the nucleus, where it executes many biological activities associated with cancer2–4. Although BAP1 was originally identified as a protein associated with the BRCA1 tumor suppressor, the significance of the BAP1 and BRCA1 interaction has thus far remained unclear4–6.  \nSeveral pioneering studies using advanced sequencing technologies have revealed a BAP1 link to human cancer. Inactivating somatic mutations have been identified in BAP1 in metastasizing uveal melanoma (UM) at a frequency of 84%, with one affected individual carrying a germline mutation7. Two human families whose members showed a high incidence of mesothelioma were reported to carry germline BAP1 mutations and sporadic mesotheliomas in individuals without germline mutations showed  \nsomatic truncation mutations of BAP1 and aberrant BAP1 expression8. In addition, 15% of patients with clear cell renal cell carcinomas (ccRCCs) were found to carry inactivating somatic BAP1 mutations, and some patients carried inactivating germline BAP1 mutations9. Subsequently, numerous studies confirmed a link between BAP1 germline mutations and a predisposition to mesothelioma10–14, UM15, 16 and ccRCC17, 18 as well as to other cancer","cbCaidg8ArIw0Zpr","https://ap.wps.com/l/cbCaidg8ArIw0Zpr","pdf",1530832,"English","# Introduction\n## BAP1 gene functions and tumor suppressor evidence\n## Links between BAP1 mutations and specific human cancers\n## BAP1 in multiprotein complexes and chromatin regulation","[{\"question\":\"What is BAP1 and why is it important for cancer biology?\",\"answer\":\"BAP1 is a deubiquitinase (deubiquitinase activity-containing protein) with broad biological functions. Somatic and germline BAP1 mutations have been identified across multiple human cancers, supporting a tumor-suppressive role.\"},{\"question\":\"Which cancers show particularly high BAP1 mutation frequency and what does this imply?\",\"answer\":\"Mesothelioma, uveal melanoma, and clear cell renal cell carcinoma show particularly high BAP1 mutation frequencies. These findings underpin the concept of BAP1-associated cancer predisposition.\"},{\"question\":\"What does the review focus on regarding BAP1 mechanisms?\",\"answer\":\"The review highlights BAP1’s roles in genome stability and apoptosis. It summarizes cellular and molecular functions in DNA repair and replication, then discusses implications for BAP1-associated cancer and therapeutic strategies.\"}]","BAP1 as a guardian of genome stability: implications in human cancer | PDF",1790220979,25]