Multiple E3s Promote the Degradation of Histone H3 Variant Cse4

Sci Rep. 2017 Aug 17;7(1):8565. doi: 10.1038/s41598-017-08923-w.

Abstract

The histone H3-like protein Cse4/CENP-A acts as a key molecular marker that differentiates the special centromeric chromatin structures from bulk nucleosomes. As altered Cse4/CENP-A activity leads to genome instability, it is pivotal to understand the mechanism underlying Cse4 regulation. Here, we demonstrate that four ubiquitin ligases (i.e., Ubr1, Slx5, Psh1, and Rcy1) work in parallel to promote Cse4 turnover in yeast. Interestingly, Cse4 overexpression leads to cellular toxicity and cell cycle delay in yeast cells lacking PSH1, but not in cells lacking UBR1, suggesting different roles of these two degradation pathways. Our findings suggest that various ubiquitin ligases collaborate to keep the Cse4 level in check, providing a basis for further delineating the intricate network involved in Cse4 regulation.

Publication types

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

MeSH terms

  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism
  • Histones / genetics
  • Histones / metabolism*
  • Mutation
  • Peptide Elongation Factors / genetics
  • Peptide Elongation Factors / metabolism
  • Proteolysis
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • CSE4 protein, S cerevisiae
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • F-Box Proteins
  • Histones
  • Peptide Elongation Factors
  • RCY1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins
  • Psh1 protein, S cerevisiae
  • UBR1 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • Slx5 protein, S cerevisiae