{"doi":"10.1101/2020.04.02.022491","title":"Subcellular localization of the J-protein Sis1 regulates the heat shock response","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>Cells exposed to heat shock induce a conserved gene expression program – the heat shock response (HSR) – encoding chaperones like Hsp70 and other protein homeostasis (proteostasis) factors. Heat shock also triggers proteostasis factors to form subcellular quality control bodies, but the relationship between these spatial structures and the HSR is unclear. Here we show that localization of the J-protein Sis1 – a co-chaperone for Hsp70 – controls HSR activation in yeast. Under nonstress conditions, Sis1 is concentrated in the nucleoplasm where it promotes Hsp70 binding to the transcription factor Hsf1, repressing the HSR. Upon heat shock, Sis1 forms an interconnected network with other proteostasis factors that spans the nucleolus and the surface of the cortical ER. We propose that localization of Sis1 to this network directs Hsp70 activity away from Hsf1 in the nucleoplasm, leaving Hsf1 free to induce the HSR. In this manner, Sis1 couples HSR activation to the spatial organization of the proteostasis network.</jats:p>\n                <jats:sec>\n                  <jats:title>One sentence summary</jats:title>\n                  <jats:p>Localization of the J-protein Sis1 to a subcellular network of proteostasis factors activates the heat shock response.</jats:p>\n                </jats:sec>","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":null,"id":22961,"datarank":0.4220743900003209,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.11015815874834542,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.11015815874834542,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":141943,"name":"Asif Ali","orcid":"0000-0001-8520-857X","position":1,"is_corresponding":false},{"id":141944,"name":"Abhyudai Singh","orcid":"0000-0002-1451-2838","position":2,"is_corresponding":false},{"id":141945,"name":"Joanna Krakowiak","orcid":"0000-0001-9873-0746","position":3,"is_corresponding":false},{"id":141947,"name":"Xu Zheng","orcid":null,"position":4,"is_corresponding":false},{"id":141949,"name":"Vytas P. Bindokas","orcid":"0000-0002-1053-2284","position":5,"is_corresponding":false},{"id":141951,"name":"Donald Wolfgeher","orcid":"0000-0002-8960-338X","position":6,"is_corresponding":false},{"id":141953,"name":"Stephen J. Kron","orcid":"0000-0003-1518-2436","position":7,"is_corresponding":false},{"id":141678,"name":"David Pincus","orcid":"0000-0002-9651-6858","position":8,"is_corresponding":false},{"id":142632,"name":"Zoe A. Feder","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21071399","pmcid":null,"openalex_id":"https://openalex.org/W3014833263","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"4DP5OD017941-04","title":"Quantitative approaches to reveal the homeostatic control mechanisms of stress re"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2020,"count":3},{"year":2021,"count":1},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/04/03/2020.04.02.022491.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/04/03/2020.04.02.022491.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2020.04.02.022491","host_type":"publisher"},{"url":"https://doi.org/10.1101/2020.04.02.022491","host_type":"repository"},{"url":"https://doi.org/10.1083/jcb.202005165","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/33326013","host_type":""},{"url":"http://dx.doi.org/10.1083/jcb.202005165","host_type":""},{"url":"https://dx.doi.org/10.1083/jcb.202005165","host_type":""},{"url":"https://dx.doi.org/10.1101/2020.04.02.022491","host_type":""},{"url":"http://dx.doi.org/10.1101/2020.04.02.022491","host_type":""}],"fields_of_study":["Heat shock proteins research","Endoplasmic Reticulum Stress and Disease","thermodynamics and calorimetric analyses"],"mesh_terms":[],"keywords":["Proteostasis","HSF1","Nucleoplasm","Nucleolus","Cell biology","Biology","Heat shock","Heat shock protein","Subcellular localization","Hsp70","Heat shock factor","Chaperone (clinical)","Transcription factor","Exoribonuclease","Genetics","Cytoplasm","Gene","RNA","Cell Nucleus","Proteasome Endopeptidase Complex","Saccharomyces cerevisiae Proteins","Saccharomyces cerevisiae","HSP40 Heat-Shock Proteins","Endoplasmic Reticulum","Models, Biological","Article","DNA-Binding Proteins","Protein Transport","Cytosol","Gene Expression Regulation, Fungal","Mutation","HSP70 Heat-Shock Proteins","Cell Nucleolus","Heat-Shock Proteins","Heat-Shock Response","Molecular Chaperones","Protein Binding","Subcellular Fractions"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T17:17:30.285432Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}