[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-383286-105":59,"doc-detail-383286-en":129},{"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":122,"head_meta":124,"extra_data":126,"updated_unix":128},105,"en","the-functional-roles-of-isg15isgylation-in-cancer-review","The Functional Roles of ISG15/ISGylation in Cancer - Review","","The protein ISG15, encoded by interferon-stimulated gene 15, is the first identified member of the ubiquitin-like protein family and exists as free monomers and conjugated complexes. ISG15 can mediate an ubiquitin-like modification, ISGylation, through covalent modification of target proteins. Evidence links both free and conjugated ISG15 to autophagy, exosome secretion, DNA repair, immune regulation, and cancer initiation and progression. The review clarifies ISG15/ISGylation functions in cancer and highlights roles that may support therapeutic intervention, while noting current research limitations and the need for further correlation studies.",{"@graph":69,"@context":121},[70,84,104],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-functional-roles-of-isg15isgylation-in-cancer-review/383286/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-functional-roles-of-isg15isgylation-in-cancer-review/383286.png","ImageObject",300,407,{"name":92,"@type":93},"anakgang17","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":4},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What is ISG15 and how is ISGylation carried out?","Question",{"text":111,"@type":112},"ISG15 is an interferon-stimulated ubiquitin-like protein that exists as free monomers or conjugated complexes. ISGylation occurs when ISG15 covalently modifies other proteins through a ubiquitin-like type of modification process.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"Which cellular processes are associated with free and conjugated ISG15?",{"text":116,"@type":112},"Both forms of ISG15 are implicated in autophagy, exosome secretion, DNA repair, and immune regulation. The review also connects ISG15 involvement to cancer occurrence and progression.",{"name":118,"@type":109,"acceptedAnswer":119},"What is the review’s main goal regarding cancer progression?",{"text":120,"@type":112},"The review aims to clarify the roles of ISG15/ISGylation in cancer, explain the important relationship between them, and emphasize new insights into how different roles may influence cancer progression. It also stresses that regulation is not fully understood and more comprehensive studies are needed.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},383286,1790255701,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":4,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":128,"read_time":36},962090883568,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","molecules   \nReview  \nThe Functional Roles of ISG15/ISGylation in Cancer  \nYin Yuan 1,†, Hai Qin 2,†, Huilong Li 1, Wanjin Shi 1, Lichen Bao 3, Shengtao Xu 1, Jun Yin 1, * and Lufeng Zheng 1, *  \n1 Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Medicinal Chemistry, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China  \n2 Department of Clinical Laboratory, Guizhou Provincial Orthopedic Hospital, No. 206, Sixian Street, Baiyun District, Guiyang 550002, China  \n3 Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing 210029, China  \n* [Correspondence: junyin@cpu.edu.cn](Correspondence: junyin@cpu.edu.cn) (J.Y.); [zhlf@cpu.edu.cn](zhlf@cpu.edu.cn) (L.Z.)† These authors contributed equally to this work.  \nAbstract: The protein ISG15 encoded by interferon-stimulated gene (ISG) 15 is the first identified member of the ubiquitin-like protein family and exists in the form of monomers and conjugated complexes. Like ubiquitin, ISG15 can mediate an ubiquitin-like modification by covalently modifying other proteins, known as ISGylation. There is growing evidence showing that both the free and conjugated ISG15 are involved in multiple key cellular processes, including autophagy, exosome secretion, DNA repair, immune regulation, and cancer occurrence and progression. In this review, we aim to further clarify the function of ISG15 and ISGylation in cancer, demonstrate the important relationship between ISG15/ISGylation and cancer, and emphasize new insights into the different roles of ISG15/ISGylation in cancer progression. This review may contribute to therapeutic intervention in cancer. However, due to the limitations of current research, the regulation of ISG15/ISGylation on cancer progression is not completely clear, thus further comprehensive and sufficient correlation studies are still needed.  \nCitation: Yuan, Y.; Qin, H.; Li, H.; Shi, W.; Bao, L.; Xu, S.; Yin, J.; Zheng, L. The Functional Roles of  \nISG15/ISGylation in Cancer. Molecules 2023, 28, 1337. [https://](https://)[ ](https://)[doi.org/10.3390/molecules28031337](doi.org/10.3390/molecules28031337)  \nAcademic Editors: Helen Osborn, Mohammad Najlahand Luca Federici  \nReceived: 16 December 2022  \nRevised: 11 January 2023  \nAccepted: 28 January 2023  \nPublished: 31 January 2023  \nCopyright: © 2023 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 ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nKeywords: ISG15; ISGylation; cancer; ubiquitin-like protein; post-translational modification  \n1. Introduction  \nPost-translational modifications (PTMs) are important for protein activities because they modulate structure and function by changing properties such as charge, hydrophilicity/hydrophobicity, and spatial structure [1].The forms of protein PTMs are various, including phosphorylation [2], ubiquitination [3], methylation [4], acetylation [5], etc. In recent years, the ubiquitin-like (UBL) modification of proteins has been extensively studied. As a PTM similar to ubiquitination, the proteins mediating UBL modification are structurally and evolutionarily related to ubiquitin. The binding of these UBL proteins to target proteins is also dependent on the level of E1 activating enzymes, E2 binding enzymes, and E3 ligases. The PTM function of UBL proteins is implicated in the nervous system [6], endocrine system [6], cardiovascular system [7], and many other diseases. Currently, the role of UBL modification in tumor occurrence and development is receiving a lot of attention [8–10](Table 1) .  \nTable 1. UBL proteins and their functions.  \n\n| UBL Proteins | E1 | E2 | E3 | Function |\n| --- | --- | --- | --- | --- |\n| UFM1 | UBA5 | UFC1 | UFL1 | Ufmylati","cbCaifmUG5qK4hWx","https://ap.wps.com/l/cbCaifmUG5qK4hWx","pdf",3830751,16,"English","# Introduction\n## Post-translational modifications (PTMs) and ubiquitin-like (UBL) modifications\n## UBL proteins and their functions\n# ISG15 biology and discovery\n## ISG15 expression, processing, and structural features\n## ISG15 covalent binding and functional distinction from ubiquitin","[{\"question\":\"What is ISG15 and how is ISGylation carried out?\",\"answer\":\"ISG15 is an interferon-stimulated ubiquitin-like protein that exists as free monomers or conjugated complexes. ISGylation occurs when ISG15 covalently modifies other proteins through a ubiquitin-like type of modification process.\"},{\"question\":\"Which cellular processes are associated with free and conjugated ISG15?\",\"answer\":\"Both forms of ISG15 are implicated in autophagy, exosome secretion, DNA repair, and immune regulation. The review also connects ISG15 involvement to cancer occurrence and progression.\"},{\"question\":\"What is the review’s main goal regarding cancer progression?\",\"answer\":\"The review aims to clarify the roles of ISG15/ISGylation in cancer, explain the important relationship between them, and emphasize new insights into how different roles may influence cancer progression. It also stresses that regulation is not fully understood and more comprehensive studies are needed.\"}]","The Functional Roles of ISG15/ISGylation in Cancer - Review | PDF"]