[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332054-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-332054-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","roles-of-post-translational-modifications-of-uhrf1-in-cancer","Roles of post-translational modifications of UHRF1 in cancer","","UHRF1, a RING-finger type E3 ubiquitin ligase family member, functions as an epigenetic regulator containing five structural domains that coordinate DNA replication, DNA methylation, and DNA damage repair. Aberrant UHRF1 overexpression is reported in more than ten cancer types, driving oncogenic transcriptional repression of tumor-suppressor genes such as CDKN2A, BRCA1, and CDH1 via DNMT1-mediated DNA methylation. Post-translational modifications including phosphorylation, acetylation, methylation, and ubiquitination further shape UHRF1 protein stability, localization, and partner interactions, with additional novel PTM types emerging whose mechanisms remain to be clarified.",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/roles-of-post-translational-modifications-of-uhrf1-in-cancer/332054/",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/roles-of-post-translational-modifications-of-uhrf1-in-cancer/332054.png","ImageObject",300,407,{"name":42,"@type":43},"Aurora","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",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 roles do post-translational modifications (PTMs) play in UHRF1-driven cancer?","Question",{"text":63,"@type":64},"PTMs regulate UHRF1 protein stability, histone methyltransferase-related activity, intracellular localization, and interactions with binding partners, contributing to abnormal UHRF1 overexpression in cancer tissues.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does UHRF1 overexpression suppress tumor-suppressor gene transcription?",{"text":68,"@type":64},"UHRF1 overexpression represses transcription of tumor-suppressor genes such as CDKN2A, BRCA1, and CDH1 through DNMT1-mediated DNA methylation.",{"name":70,"@type":61,"acceptedAnswer":71},"Why is UHRF1 considered a typical oncogene?",{"text":72,"@type":64},"UHRF1 is reported to be overexpressed in more than ten cancer types, and it plays a critical role in cancer initiation and progression as an oncogenic regulator.","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},332054,1790169728,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,119,122,126],{"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":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"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":112,"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":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},4810365810221,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Gu et al. Epigenetics & Chromatin (2024) 17:15 [https://doi.org/10.1186/s13072-024-00540-y](https://doi.org/10.1186/s13072-024-00540-y)  \nEpigenetics & Chromatin  \n REVIEW Open Access  \nRoles of post-translational modifications of UHRF1 in cancer  \nLili Gu1,2,3, Yongming Fu1,2,3 and Xiong Li 1,2,3,4*  \nAbstract  \nUHRF1 as a member of RING-finger type E3 ubiquitin ligases family, is an epigenetic regulator with five structural domains. It has been involved in the regulation of a series of biological functions, such as DNA replication, DNA methylation, and DNA damage repair. Additionally, aberrant overexpression of UHRF1 has been observed in over ten cancer types, indicating that UHRF1 is a typical oncogene. The overexpression of UHRF1 repressed the transcription of such tumor-suppressor genes as CDKN2A, BRCA1, and CDH1 through DNMT1-mediated DNA methylation. In addition to the upstream transcription factors regulating gene transcription, post-translational modifications (PTMs) also contribute to abnormal overexpression of UHRF1 in cancerous tissues. The types of PTM include phosphorylation, acetylation, methylationand ubiquitination, which regulate protein stability, histone methyltransferase activity, intracellular localization and the interaction with binding partners. Recently, several novel PTM types of UHRF1 have been reported, but the detailed mechanisms remain unclear. This comprehensive review summarized the types of UHRF1 PTMs, as well as their biological functions. A deep understanding of these crucial mechanisms of UHRF1 is pivotal for the development of novel UHRF1-targeted anti-cancer therapeutic strategies in the future.  \nKeywords PTMs, UHRF1, Protein stability, Biological functions, Drug targets  \nIntroduction  \nUHRF1 (Ubiquitin-like with PHD and RING Finger domains 1) is a member of the UHRF protein family [1]. UHRF1 is an epigenetic coordinator bridging DNA methylation and histone modifications, and has been involved in the regulation of a series of biological functions [2], such as DNA replication, DNA methylation,  \n*Correspondence: Xiong Li[lixiong@gdpu.edu.cn](lixiong@gdpu.edu.cn)  \n1 Key Laboratory of Clinical Precision Pharmacy of Guangdong Higher Education Institutes, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou 510699, Guangdong, China  \n2 Key Specialty of Clinical Pharmacy, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou 510699, Guangdong, China  \n3 NMPA Key Laboratory for Technology Research and Evaluation of Pharmacovigilance, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China  \n4 School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China  \nand DNA damage repair. Aberrant overexpression of UHRF1 has been reported in more than ten cancer types, indicating that UHRF1 is a typical oncogene, and plays a critical role in the cancer initiation and progression. Initially, murine UHRF1 (also known as NP95) was identified as a nuclear protein associated with cell proliferation [3], and later human UHRF1 (also known as ICBP90) was found to be a transcriptional regulator of topoisomerase II, which is highly expressed in the proliferating cells, especially in the malignant cells [4].UHRF1 protein is composed of five functional domains, including N-terminal ubiquitin-like domain (UBL domain), Tandem Tudor domain (TTD), plant homeodomain (PHD) finger, SET and RING associated (SRA), and C-terminal really interesting new gene (RING) finger domains. The UBL domain recruits E2-Ub and plays a crucial guiding role in specifically transferring Ub from the E2 ubiquitin binding enzyme/ubiquitin complex to histone H3 [5]. The TTD domain links DNA methylation and histone modifications by binding to H3K9me2/3 [6]. Studies have shown  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, d","cbCain9YLdkVxXqy","https://ap.wps.com/l/cbCain9YLdkVxXqy","pdf",2141481,13,"English","# Introduction\n## UHRF1 as an epigenetic regulator\n## Domain architecture and molecular functions\n## Aberrant UHRF1 overexpression in cancer\n## Post-translational modifications (PTMs) of UHRF1\n# Abstract\n## Oncogenic mechanisms driven by PTMs\n## Therapeutic implications","[{\"question\":\"What roles do post-translational modifications (PTMs) play in UHRF1-driven cancer?\",\"answer\":\"PTMs regulate UHRF1 protein stability, histone methyltransferase-related activity, intracellular localization, and interactions with binding partners, contributing to abnormal UHRF1 overexpression in cancer tissues.\"},{\"question\":\"How does UHRF1 overexpression suppress tumor-suppressor gene transcription?\",\"answer\":\"UHRF1 overexpression represses transcription of tumor-suppressor genes such as CDKN2A, BRCA1, and CDH1 through DNMT1-mediated DNA methylation.\"},{\"question\":\"Why is UHRF1 considered a typical oncogene?\",\"answer\":\"UHRF1 is reported to be overexpressed in more than ten cancer types, and it plays a critical role in cancer initiation and progression as an oncogenic regulator.\"}]","Roles of post-translational modifications of UHRF1 in cancer | PDF",1789996503,33]