Regulation of the anaphase-promoting complex by the dual specificity phosphatase human Cdc14a

J Biol Chem. 2001 Dec 21;276(51):48237-42. doi: 10.1074/jbc.M108126200. Epub 2001 Oct 11.

Abstract

Two forms of the anaphase-promoting complex (APC) mediate the degradation of critical cell cycle regulators. APC(Cdc20) promotes sister-chromatid separation by ubiquitinating securin, whereas APC(Cdh1) ubiquitinates mitotic cyclins, allowing the exit from mitosis. Here we show that phosphorylation of human Cdh1 (hCdh1) by cyclin B-Cdc2 alters the conformation of hCdh1 and prevents it from activating APC. A human homologue of yeast Cdc14, human Cdc14a (hCdc14a), dephosphorylates hCdh1 and activates APC(Cdh1). In contrast, hCdc14a does not affect the activity of APC(Cdc20). hCdc14a is a major phosphatase for hCdh1 and localizes to centrosomes in HeLa cells. Therefore, hCdc14a may promote the activation of APC(Cdh1) and exit from mitosis in mammalian cells.

Publication types

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

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • CDC2 Protein Kinase / metabolism
  • Centrosome / enzymology
  • Cyclin B / metabolism
  • Cyclin B1
  • HeLa Cells
  • Humans
  • Ligases / metabolism
  • Ligases / physiology*
  • Phosphoric Monoester Hydrolases / physiology*
  • Phosphorylation
  • Protein Tyrosine Phosphatases
  • Substrate Specificity
  • Ubiquitin-Protein Ligase Complexes*
  • Ubiquitin-Protein Ligases

Substances

  • CCNB1 protein, human
  • Cyclin B
  • Cyclin B1
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • CDC2 Protein Kinase
  • Phosphoric Monoester Hydrolases
  • CDC14A protein, human
  • Protein Tyrosine Phosphatases
  • Ligases