Romain Forey, Charlène Raclot, Cyril Pulver, Olga Rosspopoff, Sandra Offner, Julien Duc, Evarist Planet, Filipe Martins, Priscilla Turelli, Didier Trono
{"title":"癌细胞破坏灵长类动物特异性KRAB锌指蛋白ZNF93来控制APOBEC3B。","authors":"Romain Forey, Charlène Raclot, Cyril Pulver, Olga Rosspopoff, Sandra Offner, Julien Duc, Evarist Planet, Filipe Martins, Priscilla Turelli, Didier Trono","doi":"10.1073/pnas.2505021122","DOIUrl":null,"url":null,"abstract":"<p><p>ZNF93 is a primate-restricted Krüppel-associated box zinc finger protein responsible for repressing 20- to 12-My-old L1 transposable elements. Here, we reveal that ZNF93 also regulates the key cancer driver APOBEC3B-a mutagenic enzyme linked to tumorigenesis and cancer progression. ZNF93 depletion impairs DNA synthesis, activates replication and DNA damage checkpoints, and triggers proinflammatory phenotypes. Conversely, its overexpression enhances resistance to exogenous genotoxic stress, mirroring the effects observed with APOBEC3B depletion. ZNF93 expression correlates with cell proliferation rates and is overexpressed in many cancer types. These findings suggest that ZNF93 serves as a critical guardian of genome integrity, co-opted by cancer cells to counterbalance APOBEC3B-induced and L1-derived genomic instability and inflammation.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 34","pages":"e2505021122"},"PeriodicalIF":9.1000,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403153/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cancer cells subvert the primate-specific KRAB zinc finger protein ZNF93 to control APOBEC3B.\",\"authors\":\"Romain Forey, Charlène Raclot, Cyril Pulver, Olga Rosspopoff, Sandra Offner, Julien Duc, Evarist Planet, Filipe Martins, Priscilla Turelli, Didier Trono\",\"doi\":\"10.1073/pnas.2505021122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>ZNF93 is a primate-restricted Krüppel-associated box zinc finger protein responsible for repressing 20- to 12-My-old L1 transposable elements. Here, we reveal that ZNF93 also regulates the key cancer driver APOBEC3B-a mutagenic enzyme linked to tumorigenesis and cancer progression. ZNF93 depletion impairs DNA synthesis, activates replication and DNA damage checkpoints, and triggers proinflammatory phenotypes. Conversely, its overexpression enhances resistance to exogenous genotoxic stress, mirroring the effects observed with APOBEC3B depletion. ZNF93 expression correlates with cell proliferation rates and is overexpressed in many cancer types. These findings suggest that ZNF93 serves as a critical guardian of genome integrity, co-opted by cancer cells to counterbalance APOBEC3B-induced and L1-derived genomic instability and inflammation.</p>\",\"PeriodicalId\":20548,\"journal\":{\"name\":\"Proceedings of the National Academy of Sciences of the United States of America\",\"volume\":\"122 34\",\"pages\":\"e2505021122\"},\"PeriodicalIF\":9.1000,\"publicationDate\":\"2025-08-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403153/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Proceedings of the National Academy of Sciences of the United States of America\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1073/pnas.2505021122\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the National Academy of Sciences of the United States of America","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1073/pnas.2505021122","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Cancer cells subvert the primate-specific KRAB zinc finger protein ZNF93 to control APOBEC3B.
ZNF93 is a primate-restricted Krüppel-associated box zinc finger protein responsible for repressing 20- to 12-My-old L1 transposable elements. Here, we reveal that ZNF93 also regulates the key cancer driver APOBEC3B-a mutagenic enzyme linked to tumorigenesis and cancer progression. ZNF93 depletion impairs DNA synthesis, activates replication and DNA damage checkpoints, and triggers proinflammatory phenotypes. Conversely, its overexpression enhances resistance to exogenous genotoxic stress, mirroring the effects observed with APOBEC3B depletion. ZNF93 expression correlates with cell proliferation rates and is overexpressed in many cancer types. These findings suggest that ZNF93 serves as a critical guardian of genome integrity, co-opted by cancer cells to counterbalance APOBEC3B-induced and L1-derived genomic instability and inflammation.
期刊介绍：
The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
