{"doi":"10.1083/jcb.202005165","title":"Subcellular localization of the J-protein Sis1 regulates the heat shock response","abstract":"<jats:p>Cells exposed to heat shock induce a conserved gene expression program, the heat shock response (HSR), encoding 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 cofactor for the chaperone 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 endoplasmic reticulum. 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>","journal":"Journal of Cell Biology","year":2021,"id":22734,"datarank":1.4613963963798071,"base_score":4.110873864173311,"endowment":4.110873864173311,"self_citation_contribution":0.6166310796259968,"citation_network_contribution":0.8447653167538103,"self_endowment_contribution":0.6166310796259968,"citer_contribution":0.8447653167538103,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":47,"citers_with_citation_signal":36,"citers_with_endowment":36,"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":141942,"name":"Zoë A. Feder","orcid":"0000-0002-9681-648X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.110873864173311,"endowment":4.110873864173311,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33326013","pmcid":"PMC7748816","openalex_id":"https://openalex.org/W3113012547","authors":[],"funders":[{"funder_name":"National Institutes of Health Office of the Director","grant_id":"DP5 OD017941","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM124446","title":null},{"funder_name":"National Institutes of Health","grant_id":"4DP5OD017941-04","title":"Quantitative approaches to reveal the homeostatic control mechanisms of stress re"},{"funder_name":"University of Chicago","grant_id":"","title":null}],"total_grants":4,"fwci":2.5006,"citation_percentile":0.90347487,"influential_citations":5,"citation_trend":[{"year":2020,"count":2},{"year":2021,"count":9},{"year":2022,"count":10},{"year":2023,"count":9},{"year":2024,"count":15},{"year":2025,"count":12},{"year":2026,"count":3}],"oa_status":"green","license":"CC BY NC SA","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7748816","host_type":"repository"},{"url":"https://rupress.org/jcb/article-pdf/220/1/e202005165/1406573/jcb_202005165.pdf","host_type":"HYBRID"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7748816","host_type":"repository"},{"url":"https://rupress.org/jcb/article-pdf/doi/10.1083/jcb.202005165/1633305/jcb_202005165.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1083/jcb.202005165","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33326013","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7748816","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7748816?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/2020.04.02.022491","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","Insect and Pesticide Research","Chemistry","Biology","Medicine","Cell Nucleolus","Cell Nucleus","Cytosol","DNA-Binding Proteins","Endoplasmic Reticulum","Gene Expression Regulation, Fungal","HSP40 Heat-Shock Proteins","HSP70 Heat-Shock Proteins","Heat-Shock Proteins","Heat-Shock Response","Models, Biological","Molecular Chaperones","Mutation","Proteasome Endopeptidase Complex","Protein Binding","Protein Transport","Proteostasis","Saccharomyces cerevisiae","Saccharomyces cerevisiae Proteins","Subcellular Fractions","Transcription Factors","Transcriptome"],"mesh_terms":["Proteostasis","Cell Nucleolus","Cell Nucleus","Cytosol","DNA-Binding Proteins","Endoplasmic Reticulum","Heat-Shock Proteins","Models, Biological","Mutation","Protein Binding","Saccharomyces cerevisiae","Subcellular Fractions","Transcription Factors","Gene Expression Regulation, Fungal","Molecular Chaperones","HSP70 Heat-Shock Proteins","Heat-Shock Response","Protein Transport","Saccharomyces cerevisiae Proteins","Proteasome Endopeptidase Complex","HSP40 Heat-Shock Proteins","Transcriptome"],"keywords":["Proteostasis","HSF1","Nucleoplasm","Nucleolus","Cell biology","Heat shock","Biology","Heat shock protein","Heat shock factor","Subcellular localization","Hsp70","Endoplasmic reticulum","Transcription factor","Chaperone (clinical)","HSPA12A","Exoribonuclease","Cytoplasm","Genetics","Gene","RNA","Cell Nucleus","Proteasome Endopeptidase Complex","Saccharomyces cerevisiae Proteins","Saccharomyces cerevisiae","HSP40 Heat-Shock Proteins","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":[{"name":"geo"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T15:52:25.780194Z","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":[]}