Subcellular localization of the J-protein Sis1 regulates the heat shock response

J Cell Biol. 2021 Jan 4;220(1):e202005165. doi: 10.1083/jcb.202005165.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleolus / metabolism
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • DNA-Binding Proteins / metabolism
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation, Fungal
  • HSP40 Heat-Shock Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / metabolism
  • Heat-Shock Response*
  • Models, Biological
  • Molecular Chaperones / metabolism
  • Mutation / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding
  • Protein Transport
  • Proteostasis
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Subcellular Fractions / metabolism
  • Transcription Factors / metabolism
  • Transcriptome / genetics


  • DNA-Binding Proteins
  • HSF1 protein, S cerevisiae
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Molecular Chaperones
  • SIS1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Proteasome Endopeptidase Complex