βTrCP-mediated ubiquitylation regulates protein stability of Mis18β in a cell cycle-dependent manner

Biochem Biophys Res Commun. 2014 Jan 3;443(1):62-7. doi: 10.1016/j.bbrc.2013.11.058. Epub 2013 Nov 21.

Abstract

Ubiquitin E3 ligases including SCF complex are key regulators of cell cycle. Here, we show that Mis18β, a component of Mis18 complex governing CENP-A localization, is a new substrate of βTrCP-containing SCF complex. βTrCP interacted with Mis18β exclusively during interphase but not during mitosis and mediated proteasomal degradation of Mis18β leading to the inactivation of Mis18 complex during interphase. In addition, uncontrolled stabilization of Mis18β caused cell death. Together, we propose that βTrCP-mediated regulation of Mis18β stability is a mechanism to restrict centromere function of Mis18 complex from late mitosis to early G1 phase.

Keywords: CDK; CHX; Centromere; H3S10ph; Mis18β; Mitosis; Protein stability; SCF; Skp1/Cul1/F-box protein complex; Ubiquitylation; aa; amino acid; cyclin-dependent kinase; cycloheximide; phosphorylation at 10th serine residue of histone H3; βTrCP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Cell Cycle Proteins
  • Cell Cycle*
  • Centromere / metabolism
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • HeLa Cells
  • Humans
  • Protein Stability
  • RNA Interference
  • RNA, Small Interfering / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Ubiquitination*
  • beta-Transducin Repeat-Containing Proteins / metabolism*

Substances

  • BTRC protein, human
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • OIP5 protein, human
  • RNA, Small Interfering
  • beta-Transducin Repeat-Containing Proteins
  • SKP Cullin F-Box Protein Ligases