[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382814-105":59,"doc-detail-382814-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","mlf2-negatively-regulates-p53-and-promotes-colorectal-carcinogenesis","MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis","","MLF2 is identified as a new negative regulator of the p53 pathway in colorectal cancer. The study shows that MLF2 directly interacts with p53 and USP7, blocking USP7 binding to p53 and counteracting USP7-mediated deubiquitination, which destabilizes p53. Functionally, MLF2 promotes colorectal carcinogenesis, at least partly through negative regulation of p53. Clinically, MLF2 is elevated in colorectal cancer, high expression predicts poor prognosis, and in wild-type p53 tumors MLF2 and p53 are inversely correlated.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mlf2-negatively-regulates-p53-and-promotes-colorectal-carcinogenesis/382814/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/mlf2-negatively-regulates-p53-and-promotes-colorectal-carcinogenesis/382814.png","ImageObject",300,407,{"name":92,"@type":93},"Terk","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the role of MLF2 in p53 regulation?","Question",{"text":112,"@type":113},"MLF2 acts as a negative regulator of p53 by interfering with USP7-mediated deubiquitination, leading to p53 destabilization.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does MLF2 influence the USP7–p53 pathway?",{"text":117,"@type":113},"MLF2 interacts with both p53 and USP7, inhibits USP7 binding to p53, and antagonizes USP7’s deubiquitination activity on p53.",{"name":119,"@type":110,"acceptedAnswer":120},"What clinical associations are reported for MLF2 in colorectal cancer?",{"text":121,"@type":113},"MLF2 is elevated in colorectal cancer, and higher MLF2 expression is associated with poorer patient prognosis; in wild-type p53 tumors, MLF2 and p53 levels are inversely correlated.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},382814,1790404133,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099525198933,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","RESEARCH ARTICLE  \n[www.advancedscience.com](www.advancedscience.com)  \nMLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis  \nDebao Fang, Hao Hu, Kailiang Zhao,* Aman Xu, Changjun Yu, Yong Zhu, Ning Yu, Bo Yao, Suyun Tang, Xianning Wu, and Yide Mei*  \nInactivation of the p53 pathway is linked to a variety of human cancers. As a critical component of the p53 pathway, ubiquitin-specific protease 7 (USP7) acts as a deubiquitinase for both p53 and its ubiquitin E3 ligase mouse double minute 2 homolog. Here, myeloid leukemia factor 2 (MLF2) is reported as anew negative regulator of p53. MLF2 interacts with both p53 and USP7. Via these interactions, MLF2 inhibits the binding of USP7 to p53 and antagonizes USP7-mediated deubiquitination ofp53, thereby leading to p53 destabilization. Functionally, MLF2 plays an oncogenic role in colorectal cancer, at least partially, via the negative regulation of p53. Clinically, MLF2 is elevated in colorectal cancer and its high expression is associated with poor prognosis in patients with colorectal cancer. In wild-type-p53-containing colorectal cancer, MLF2 and p53 expressions are inversely correlated. These findings establish MLF2 as an important suppressor of p53 function. The study also reveals a critical role for the MLF2–p53 axis in promoting colorectal carcinogenesis.  \n1. Introduction  \np53 plays a prominent role in tumor prevention. [1,2] The tumor suppressive function of p53 is largely attributed to its ability to activate the expression of target genes that are involved in various cellular processes, such as cell cycle arrest, apoptosis, senescence, autophagy, ferroptosis, and cell metabolism. [3–8] In approximately half of human cancers, p53 is inactivated by either chromosomal deletion or somatic mutation. Even in tumors harboring wildtype p53, the p53 pathway is often disrupted by altered expression of upstream or downstream regulatory factors. [9,10] Moreover, germline mutations of p53 have been linked to Li-Fraumeni syndrome, a cancer predisposition disorder.[11] Therefore, inhibition of p53 activity is considered to be crucial for tumorigenesis.  \nD. Fang, K. Zhao, X. Wu, Y. Mei  \nDepartment of Thoracic Surgery, The First Affiliated Hospital of USTC Division of Life Sciences and Medicine  \nUniversity of Science and Technology of China Hefei, Anhui 230001, China  \nE-mail: [zkailiang@ustc.edu.cn](zkailiang@ustc.edu.cn); [meiyide@ustc.edu.cn](meiyide@ustc.edu.cn)  \nD. Fang, H. Hu, K. Zhao, N. Yu, B. Yao, S. Tang, Y. Mei  \nThe CAS Key Laboratory of Innate Immunity and Chronic Disease Division of Life Sciences and Medicine  \nUniversity of Science and Technology of China Hefei, Anhui 230027, China  \nA. Xu, C. Yu, Y. Zhu  \nDepartment of General Surgery  \nThe First Affiliated Hospital of Anhui Medical University Hefei, Anhui 230022, China  \nY. Mei  \nCenter for Advanced Interdisciplinary Science and Biomedicine of IHM Division of Life Sciences and Medicine  \nUniversity of Science and Technology of China Hefei, Anhui 230027, China  \nThe ORCID identification number(s) for the author(s) of this article can be found under [https://doi.org/10.1002/advs.202303336](https://doi.org/10.1002/advs.202303336)  \n© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nDOI: 10.1002/advs.202303336  \nGiven the potent antiproliferative activity of p53, its expression needs to be tightly restricted in unstressed cells. It has been well accepted that p53 expression is mainly regulated at the level of protein stability, which allows rapid p53 accumulation and activation upon stress. Under normal conditions, p53 is expressed at low levels due to the constant ubiquitination and proteasomal degradation mediated by several ubiquitin E3 ligases, among which mouse double minute 2 homolog (Mdm2) is","cbCaia2B6Jhj1zJi","https://ap.wps.com/l/cbCaia2B6Jhj1zJi","pdf",3579195,11,"English","# Introduction\n## p53 tumor-suppressive functions and inactivation\n## Regulation of p53 protein stability\n## Role of USP7 in the Mdm2–p53 pathway\n# MLF2–p53 interaction and functional consequences\n## Clinical relevance in colorectal cancer","[{\"question\":\"What is the role of MLF2 in p53 regulation?\",\"answer\":\"MLF2 acts as a negative regulator of p53 by interfering with USP7-mediated deubiquitination, leading to p53 destabilization.\"},{\"question\":\"How does MLF2 influence the USP7–p53 pathway?\",\"answer\":\"MLF2 interacts with both p53 and USP7, inhibits USP7 binding to p53, and antagonizes USP7’s deubiquitination activity on p53.\"},{\"question\":\"What clinical associations are reported for MLF2 in colorectal cancer?\",\"answer\":\"MLF2 is elevated in colorectal cancer, and higher MLF2 expression is associated with poorer patient prognosis; in wild-type p53 tumors, MLF2 and p53 levels are inversely correlated.\"}]","MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis | PDF",1790252527,28]