Cdh1 degradation is mediated by APC/C-Cdh1 and SCF-Cdc4 in budding yeast

Biochem Biophys Res Commun. 2018 Dec 2;506(4):932-938. doi: 10.1016/j.bbrc.2018.10.179. Epub 2018 Nov 2.

Abstract

Cdh1, a substrate-recognition subunit of anaphase-promoting complex/cyclosome (APC/C), is a tumor suppressor, and it is downregulated in various tumor cells in humans. APC/C-Cdh1 is activated from late M phase to G1 phase by antagonizing Cdk1-mediated inhibitory phosphorylation. However, how Cdh1 protein levels are properly regulated is ill-defined. Here we show that Cdh1 is degraded via APC/C-Cdh1 and Skp1-Cullin1-F-box (SCF)-Cdc4 in the budding yeast Saccharomyces cerevisiae. Cdh1 degradation was promoted by forced localization of Cdh1 into the nucleus, where APC/C and SCF are present. Cdk1 promoted APC/C-Cdh1-mediated Cdh1 degradation, whereas polo kinase Cdc5 elicited SCF-Cdc4-mediated degradation. Thus, Cdh1 degradation is controlled via multiple pathways.

Keywords: APC/C; CDK; Cdh1; Polo kinase; SCF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Cdh1 Proteins / chemistry
  • Cdh1 Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • F-Box Proteins / metabolism*
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomycetales / metabolism*
  • Structure-Activity Relationship
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • CDC4 protein, S cerevisiae
  • CDH1 protein, S cerevisiae
  • Cdh1 Proteins
  • Cell Cycle Proteins
  • F-Box Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex