[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-343821-105":59,"doc-detail-343821-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","targeting-chaperone-modifications-innovative-approaches-to-cancer-treatment","Targeting chaperone modifications: Innovative approaches to cancer treatment","","Reviewing alterations in the protein quality control system, the article explains how cellular chaperones (heat shock proteins, HSPs) perform protein triage that can determine protein fate after binding. It synthesizes advances on regulatory mechanisms and posttranslational modifications shaping interactions, function, and localization, emphasizing key components of the heat shock response. The focus is a mechanistic shift in co-chaperone engagement—from heat shock protein organizing protein to carboxyl-terminus of HSC70 interacting protein—linked with HSP70 and HSP90. The review connects activation factors, chaperones, and co-chaperones to disease-driven regulation and therapeutically targetable strategies.",{"@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/targeting-chaperone-modifications-innovative-approaches-to-cancer-treatment/343821/",{"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/targeting-chaperone-modifications-innovative-approaches-to-cancer-treatment/343821.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the role of cellular chaperones in the protein quality control system?","Question",{"text":112,"@type":113},"Cellular chaperones, also called heat shock proteins (HSPs), perform protein triage and help determine the fate of proteins they bind to, influencing refolding or degradation decisions.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the heat shock response system (HSR) regulate cellular stress?",{"text":117,"@type":113},"The HSR integrates molecular chaperones, co-chaperones, transcription factors, and cofactors to manage protein homeostasis and respond to multiple stressors such as heat, oxidative stress, metabolic stress, and hypoxia.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is the co-chaperone engagement shift important for cancer relevance?",{"text":121,"@type":113},"The review highlights a mechanistic transition in co-chaperone engagement—from heat shock protein organizing protein to carboxyl-terminus of HSC70 interacting protein—associated with HSP70 and HSP90, which can influence cellular growth and survival pathways.","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},343821,1790142079,{"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":8,"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},962075114765,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","REVIEW  \nTargeting chaperone modifications: Innovative approaches to cancer treatment  \nReceived for publication, May 28, 2024, and in revised form, October 9, 2024 Published, Papers in Press, October 19, 2024, [https://doi.org/10.1016/j.jbc.2024.107907](https://doi.org/10.1016/j.jbc.2024.107907)  \nMariah Stewart 1 and Jonathan C. Schisler 1,2, *  \nFrom the 1The McAllister Heart Institute and Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 2The Department of Pathology and Lab Medicine and Computational Medicine Program, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA  \nReviewed by members of the JBC Editorial Board. Edited by George DeMartino  \nCancer and other chronic diseases are marked by alterations in the protein quality control system, affecting the posttranslational destiny of various proteins that regulate, structure, and catalyze cellular processes. Cellular chaperones, also known as heat shock proteins (HSPs), are pivotal in this system, performing protein triage that often determines the fate of proteins they bind to. Grasping the regulatory mechanisms of HSPs and their associated cofactors is crucial for understanding protein quality control in both healthy and diseased states. Recent research has shed light on the interactions within the protein quality control system and how post-translational modification govern protein interactions, function, and localization, which can drive or inhibit cell proliferation. This body of work encompasses critical elements of the heat shock response, including heat shock protein 70, heat shock protein 90, carboxyl-terminus of HSC70 interacting protein, and heat shock protein organizing protein. This review aims to synthesize these advancements, offering a holistic understanding of the system and its response when commandeered by diseases like cancer. We focus on the mechanistic shift in co-chaperone engagement—transitioning from heat shock protein organizing protein to carboxyl-terminus of HSC70 interacting protein in association with heat shock protein 70 and heat shock protein 90—which could influence cellular growth and survival pathways. A comprehensive examination of posttranslational modification–driven regulation within the protein quality control network is presented, highlighting the roles of activation factors, chaperones, and co-chaperones. Our insights aim to inform new strategies for therapeutically targeting diseases by considering the entire heat shock response system.  \nProtein quality control and the heat shock response system  \nThe cellular protein quality control (PQC) system is a complex network of enzymes and organelles crucial for maintaining cellular functions and responding to various stressors (1, 2). Within the PQC system, the heat shock response system (HSR) is critical in managing cellular stress,  \n* Address For correspondence: Jonathan C. Schisler, [schisler@unc.edu](schisler@unc.edu).  \nincluding heat, oxidative, metabolic, and hypoxia (3). The HSR operates through a sophisticated interplay of molecular chaperones, co-chaperones, transcription factors, and cofactors to ensure protein homeostasis and effectively respond to stressors (4). Central to the HSR are molecular chaperones like heat shock protein 70 (HSP70) and heat shock protein 90 (HSP90), which work in concert with co-chaperones to triage proteins for refolding or degradation (Fig. 1A) (5–7).  \nThe HSRisfinely regulated by transcription factors such as heat shock factor 1 (HSF1), which orchestrates the transcriptional response to stress by upregulating various chaperones(8, 9). Upon stress induction, HSF1 changes protein–protein interactions and post-translational modifications (PTMs), leading to its activation and subsequent binding to DNA to promote the transcription of HSR proteins (Fig. 1B) (10). Notably, a negative feedback loop involving the chaperone HSP70 and co-chaperone heat shock protein 40","cbCaiiXQ71GdFQFm","https://ap.wps.com/l/cbCaiiXQ71GdFQFm","pdf",1500058,18,"English","# Protein quality control and the heat shock response system\n## Overview of the PQC and HSR network\n## Core HSR components and stress regulation\n## Transcriptional control and feedback loops\n## Posttranslational modifications shaping HSR\n## Chaperone complexes and downstream degradation pathways\n## Stress adaptability beyond heat","[{\"question\":\"What is the role of cellular chaperones in the protein quality control system?\",\"answer\":\"Cellular chaperones, also called heat shock proteins (HSPs), perform protein triage and help determine the fate of proteins they bind to, influencing refolding or degradation decisions.\"},{\"question\":\"How does the heat shock response system (HSR) regulate cellular stress?\",\"answer\":\"The HSR integrates molecular chaperones, co-chaperones, transcription factors, and cofactors to manage protein homeostasis and respond to multiple stressors such as heat, oxidative stress, metabolic stress, and hypoxia.\"},{\"question\":\"Why is the co-chaperone engagement shift important for cancer relevance?\",\"answer\":\"The review highlights a mechanistic transition in co-chaperone engagement—from heat shock protein organizing protein to carboxyl-terminus of HSC70 interacting protein—associated with HSP70 and HSP90, which can influence cellular growth and survival pathways.\"}]","Targeting chaperone modifications: Innovative approaches to cancer treatment | PDF",1790052251,45]