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As a transcription factor with two separate DNA-binding domains, it can positively regulate gene expression. PAX3 activity is shaped by upstream pathways and downstream protein interactions, including posttranscriptional modifications. During disease progression, PAX3 pathways may be subverted, with overexpression reported in melanoma, neuroblastoma, and rhabdomyosarcoma.",{"@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/pax3-a-driver-of-normal-development-and-disease/355345/",{"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/pax3-a-driver-of-normal-development-and-disease/355345.png","ImageObject",300,407,{"name":92,"@type":93},"\tJames","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What biological processes does PAX3 regulate during normal development?","Question",{"text":112,"@type":113},"PAX3 regulates proper growth, migration, differentiation, and survival of developing tissues, including those derived from the embryonic neural crest.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does PAX3 control gene expression?",{"text":117,"@type":113},"PAX3 is a transcription factor with two DNA-binding domains, enabling it to bind DNA sequences and cooperate with other factors to regulate target gene transcription.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence links PAX3 to cancer?",{"text":121,"@type":113},"PAX3 is overexpressed in multiple cancers, including melanoma, neuroblastoma, and rhabdomyosarcoma, and it is implicated in regulating survival, migration, invasion, and proliferation.","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},355345,1790451765,{"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":44,"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},2336474466412,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Review  \nPAX3: A Driver of Normal Development and Disease Noah B. Prince, Joyce H. Liang, Theresa M. Rosato and Deborah Lang *  \nAcademic Editor: AthanasiaMouzaki  \nReceived: 23 December 2025  \nRevised: 10 March 2026  \nAccepted: 13 March 2026  \nPublished: 17 March 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \nDepartment of Dermatology, Boston University, Boston, MA 02118, USA; [nbprince@bu.edu](nbprince@bu.edu) (N.B.P.);  \n[jhrliang@bu.edu](jhrliang@bu.edu) (J.H.L.); [tmrosato@bu.edu](tmrosato@bu.edu) (T.M.R.)  \n* Correspondence: [deblang@bu.edu](deblang@bu.edu); Tel.: +1-617-358-9721  \nAbstract  \nPAX3 plays a vital role in regulating proper growth, migration, differentiation, and survival during development of normal tissues, including those derived from the embryonic neural crest. PAX3 is a transcription factor with two separate DNA-binding domains and can positively (and less frequently, negatively) regulate gene expression. The levels of PAX3 can be modified by upstream molecular pathways, and its subsequent downstream functions are regulated through a wide range of protein interactions and posttranscriptional modifications. PAX3 direct downstream target genes are other transcription regulators and factors that modulate cellular proliferation, lineage specificity, migration, and survival. The pathways that PAX3 regulates during development may be recycled and subverted during disease progression, for example, during cancer progression, growth, and metastasis. Indeed, PAX3 is overexpressed in several cancers, including melanoma, neuroblastoma, and rhabdomyosarcoma. While there is still much that is unknown about the mechanisms by which PAX3 controls such a wide array of key cellular functions, a great deal of progress has been made to advance our understanding of this critical and multi-faceted factor.  \nKeywords: PAX3; melanocyte; melanoma; neural crest; PAX proteins; transcription factor  \n1. Introduction  \nPaired Box 3 (PAX3), also known as HUP2, WS1, WS3, or CDHS, is a transcription factor that plays important roles in both normal development and pathogenesis. PAX3 is a member of the 9-gene PAX family, which is characterized by the highly conserved paired box domain but with greater variations in other regions of the protein between family members [1] . PAX3 also contains a homeodomain, and the interplay between these two DNA-binding domains allows PAX3 tobind a wide range of DNA sequences to regulate transcription of many vital genes, especially during development. This complexity is further expanded by PAX3’s ability to cooperatively bind other factors to enhance transcription of target genes, increasing the number of interactions PAX3 can participate in to regulate gene expression.  \nGiven the large number of possible interactions and downstream targets of PAX3 activity, PAX3 is subject to a high degree of transcriptional regulation itself. As a gene that is primarily expressed during development in normal states, PAX3 lies downstream of several prominent developmental pathways. It is transcriptionally promoted by effectors of the Hippo and Wnt/β-catenin pathways and repressed by effectors of the Sonic hedge hog (Shh) and TGFβ pathways. Through the interactions of these opposing pathways, PAX3 expression is maintained in the neural crest, central nervous system, and somites during development, before being downregulated in most tissues as cells undergo terminal differentiation.  \nDuring embryogenesis, PAX3 directs the expression of a large number of genes that influence the development of the tissues in which it is active. PAX3’s target genes are best characterized in the developing neural crest, melanocytes, and myocytes. In these tissues, PAX3 promotes the expression of genes that influence differentiation, proliferation, and migration, and is essenti","cbCaiiSshZgYXQWY","https://ap.wps.com/l/cbCaiiSshZgYXQWY","pdf",1780107,25,"English","# Abstract\n# 1. Introduction\n# 2. PAX3 Structure and Post-Translational Modifications","[{\"question\":\"What biological processes does PAX3 regulate during normal development?\",\"answer\":\"PAX3 regulates proper growth, migration, differentiation, and survival of developing tissues, including those derived from the embryonic neural crest.\"},{\"question\":\"How does PAX3 control gene expression?\",\"answer\":\"PAX3 is a transcription factor with two DNA-binding domains, enabling it to bind DNA sequences and cooperate with other factors to regulate target gene transcription.\"},{\"question\":\"What evidence links PAX3 to cancer?\",\"answer\":\"PAX3 is overexpressed in multiple cancers, including melanoma, neuroblastoma, and rhabdomyosarcoma, and it is implicated in regulating survival, migration, invasion, and proliferation.\"}]","PAX3: A Driver of Normal Development and Disease | PDF",1790117941,63]