[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-447914-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-447914-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":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","erk-phosphorylates-hnrnpf-to-promote-the-proliferation-and-suppress-the-differentiation-of-embryonic-stem-cells","ERK phosphorylates HNRNPF to promote the proliferation and suppress the differentiation of embryonic stem cells","","The mitogen-activated extracellular signal-regulated kinase/extracellular signal-regulated kinase (MEK/ERK) pathway shows a dual influence on embryonic stem cell (ESC) self-renewal and differentiation. ERK2 was shown to phosphorylate HNRNPF on Ser346 and Tyr356. Hnrnpf knockout lowers ESC proliferation by downregulating CDK1 and CCNB1 and increases differentiation through reduced EED. Phospho-mimetic HNRNPF more effectively rescues growth and suppresses mesodermal and trophectodermal differentiation. Mechanistically, HNRNPF binds Cdk1, Ccnb1, and Eed mRNAs to enhance translation, with phosphorylation strengthening these interactions.",{"@graph":14,"@context":72},[15,34,55],{"@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/erk-phosphorylates-hnrnpf-to-promote-the-proliferation-and-suppress-the-differentiation-of-embryonic-stem-cells/447914/",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/erk-phosphorylates-hnrnpf-to-promote-the-proliferation-and-suppress-the-differentiation-of-embryonic-stem-cells/447914.png","ImageObject",300,407,{"name":42,"@type":43},"Finn","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-06","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":30},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"Which residues does ERK2 phosphorylate on HNRNPF?","Question",{"text":62,"@type":63},"ERK2 phosphorylates HNRNPF on Ser346 and Tyr356.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"What happens to ESC proliferation and differentiation when Hnrnpf is knocked out?",{"text":67,"@type":63},"Hnrnpf knockout reduces ESC proliferation rate and promotes differentiation, attributed to reduced EED.",{"name":69,"@type":60,"acceptedAnswer":70},"How does phosphorylated HNRNPF regulate gene expression?",{"text":71,"@type":63},"Phosphorylated HNRNPF binds Cdk1, Ccnb1, and Eed mRNAs, enhancing their translation efficiency; phosphorylation strengthens binding and translation.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},447914,1791158970,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"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":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"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":30,"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},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","Nucleic Acids Research, 2026, 54, gkaf1490 [https://doi.org/10.1093/nar/gkaf1490](https://doi.org/10.1093/nar/gkaf1490)  \n[RNA and RNA-protein complexes](RNA and RNA-protein complexes)  \nERK phosphorylates HNRNPF to promote the proliferation and suppress the differentiation of embryonic stem cells  \nXiaowei Duan 1 , Yuying Wang1 , Jingai Zhang1 , Nannan Zhao1 , Qianyi Hao1 , Xiaoqiong Yang1 , Xiaoling Du1 , Hongjie Yang2 , Huabin Liang 1 ,* , Lingyi Chen 1 ,*  \n1 State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Frontiers Science Center for Cell Responses, National Demonstration Center for Experimental Biology Education and College of Life Sciences, Nankai University, Tianjin 300071, China  \n2 Department of Colorectal Surgery, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin 300121, China  \n∗ To whom correspondence should be addressed. Email: [lingyichen@nankai.edu.cn](lingyichen@nankai.edu.cn)  \nCorrespondence may also be addressed to Huabin Liang. Email: [huabinliang@nankai.edu.cn](huabinliang@nankai.edu.cn)  \nAbstract  \nThe mitogen-activated extracellular signal-regulated kinase/extracellular signal-regulated kinase (MEK/ERK) signaling plays a dual role in regulating the self-renewal and differentiation of embryonic stem cells (ESCs) . How MEK/ERK promotes ESC self-renewal remains elusive, while the mechanisms for MEK/ERK to stimulate ESC differentiation have been investigated extensively. Here, we demonstrated that ERK2 phosphorylatesheterogenous nuclear ribonucleoprotein F (HNRNPF) on Ser346 and Tyr356 . Hnrnpf knockout reduces ESC proliferation rate, through downregulating CDK1 and CCNB1, and promotes ESC differentiation, attributed to reduced EED. Moreover, compared with the unphospho-mimetic mutant, the phospho-mimetic HNRNPF is more potent in rescuing ESC growth, as well as suppressing the mesodermal and trophectodermal differentiation. Mechanistically, HNRNPF binds to Cdk1 , Ccnb1 , and Eed messenger RNAs (mRNAs), thereby enhancing their translation efficiency. Additionally, phosphorylation of HNRNPF enhances its binding to these mRNAs and promotes their translation. Taken together, ERK may facilitate ESC proliferation and suppress lineage differentiation through phosphorylating HNRNPF.  \nGraphical abstract  \nIntroduction  \nEmbryonic stem cells (ESCs), derived from the inner cell mass of pre-implantation blastocysts, possess unlimited proliferation capacity and the potential to differentiate into all somatic cell types, namely pluripotency. Elucidating the underlying molecular mechanisms that govern these properties is beneficial for the therapeutic application of ESCs in regenerative medicine [1, 2] .  \nThe mitogen-activated extracellular signal-regulated kinase/extracellular signal-regulated kinase (MEK/ERK) signaling regulates numerous cellular activities, including cell cycle progression, proliferation, and differentiation [3–5] . It is well  \nrecognized that MEK/ERK signaling is essential for the differentiation of ESCs and detrimental for ESC self-renewal. Activation of MEK/ERK signaling leads to ESC differentiation [6–8], while simultaneous inhibition of MEK and GSK3 facilitates the maintenance of naïve pluripotency [9] . In addition, MEK inhibition is widely applied in culturing primate and human naïve ESCs [10–15] . Multiple mechanisms for MEK/ERK to suppress ESC self-renewal and promote ESC differentiation have been revealed. First, ERK phosphorylatespluripotency factors NANOG and KLF4, accelerating the degradation of these proteins and thus compromising the selfrenewal of ESCs [16–18]. Second, phosphorylation of another  \nReceived: July 17, 2025. Revised: December 11, 2025. Accepted: December 15, 2025  \n© The Author(s) 2026. Published by Oxford University Press.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License  \n([https://creativecommons.org/licenses/b","cbCaiuNJrlRaaLDj","https://ap.wps.com/l/cbCaiuNJrlRaaLDj","pdf",4203105,13,"English","# Abstract\n# Introduction\n## MEK/ERK signaling roles in ESC pluripotency\n## Known ERK mechanisms affecting self-renewal and differentiation","[{\"question\":\"Which residues does ERK2 phosphorylate on HNRNPF?\",\"answer\":\"ERK2 phosphorylates HNRNPF on Ser346 and Tyr356.\"},{\"question\":\"What happens to ESC proliferation and differentiation when Hnrnpf is knocked out?\",\"answer\":\"Hnrnpf knockout reduces ESC proliferation rate and promotes differentiation, attributed to reduced EED.\"},{\"question\":\"How does phosphorylated HNRNPF regulate gene expression?\",\"answer\":\"Phosphorylated HNRNPF binds Cdk1, Ccnb1, and Eed mRNAs, enhancing their translation efficiency; phosphorylation strengthens binding and translation.\"}]","ERK phosphorylates HNRNPF to promote the proliferation and suppress the differentiation of embryonic stem cells | PDF",1790724019,33]