Cdc48 regulates intranuclear quality control sequestration of the Hsh155 splicing factor in budding yeast

J Cell Sci. 2020 Dec 3;133(23):jcs252551. doi: 10.1242/jcs.252551.

Abstract

Cdc48 (known as VCP in mammals) is a highly conserved ATPase chaperone that plays an essential role in the assembly and disassembly of protein-DNA complexes and in degradation of misfolded proteins. We find that in Saccharomyces cerevisiae budding yeast, Cdc48 accumulates during cellular stress at intranuclear protein quality control sites (INQ). We show that Cdc48 function is required to suppress INQ formation under non-stress conditions and to promote recovery following genotoxic stress. Cdc48 physically associates with the INQ substrate and splicing factor Hsh155, and regulates its assembly with partner proteins. Accordingly, cdc48 mutants have defects in splicing and show spontaneous distribution of Hsh155 to INQ aggregates, where it is stabilized. Overall, this study shows that Cdc48 regulates deposition of proteins at INQ and suggests a previously unknown role for Cdc48 in the regulation or stabilization of splicing subcomplexes.This article has an associated First Person interview with the first author of the paper.

Keywords: Cdc48; Hsh155; INQ; Protein quality control; Splicing; Yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • RNA Splicing Factors
  • Ribonucleoprotein, U2 Small Nuclear*
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Valosin Containing Protein* / genetics

Substances

  • Cell Cycle Proteins
  • HSH155 protein, S cerevisiae
  • RNA Splicing Factors
  • Ribonucleoprotein, U2 Small Nuclear
  • Saccharomyces cerevisiae Proteins
  • CDC48 protein, S cerevisiae
  • Valosin Containing Protein

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