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

Zoë A Feder; Asif Ali; Abhyudai Singh; Joanna Krakowiak; Xu Zheng; Vytas P Bindokas; Donald Wolfgeher; Stephen J Kron; David Pincus

doi:10.1083/jcb.202005165

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.

Authors

Zoë A Feder^#¹, Asif Ali^#², Abhyudai Singh^{3

4

5

6}, Joanna Krakowiak¹, Xu Zheng^{1

7}, Vytas P Bindokas⁸, Donald Wolfgeher², Stephen J Kron², David Pincus^{1

2

9}

Affiliations

¹ Whitehead Institute for Biomedical Research, Cambridge, MA.
² Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL.
³ Department of Electrical and Computer Engineering, University of Delaware, Newark, DE.
⁴ Department of Biomedical Engineering, University of Delaware, Newark, DE.
⁵ Department of Mathematical Sciences, University of Delaware, Newark, DE.
⁶ Center for Bioinformatics and Computational Biology, University of Delaware, Newark, DE.
⁷ State Key Laboratory of Wheat and Maize Crop Science, College of Agronomy, Henan Agricultural University, Zhengzhou, China.
⁸ Integrated Light Microscopy Core Facility, University of Chicago, Chicago, IL.
⁹ Center for Physics of Evolving Systems, University of Chicago, Chicago, IL.

^# Contributed equally.

Abstract

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

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding