Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells

J Cell Biol. 2004 Jan 19;164(2):233-41. doi: 10.1083/jcb.200309035.

Abstract

We have found that key mitotic regulators show distinct patterns of degradation during exit from mitosis in human cells. Using a live-cell assay for proteolysis, we show that two of these regulators, polo-like kinase 1 (Plk1) and Aurora A, are degraded at different times after the anaphase-promoting complex/cyclosome (APC/C) switches from binding Cdc20 to Cdh1. Therefore, events in addition to the switch from Cdc20 to Cdh1 control the proteolysis of APC/C(Cdh1) substrates in vivo. We have identified a putative destruction box in Plk1 that is required for degradation of Plk1 in anaphase, and have examined the effect of nondegradable Plk1 on mitotic exit. Our results show that Plk1 proteolysis contributes to the inactivation of Plk1 in anaphase, and that this is required for the proper control of mitotic exit and cytokinesis. Our experiments reveal a role for APC/C-mediated proteolysis in exit from mitosis in human cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase / physiology*
  • Anaphase-Promoting Complex-Cyclosome
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cdc20 Proteins
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / metabolism
  • Cloning, Molecular
  • Endopeptidases / metabolism*
  • Genes, Reporter
  • HeLa Cells / cytology
  • Humans
  • Kinetics
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Lysosomes / ultrastructure
  • Mitosis / physiology
  • Polo-Like Kinase 1
  • Protein Kinase Inhibitors*
  • Protein Kinases*
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Recombinant Proteins / metabolism
  • Ubiquitin-Protein Ligase Complexes / metabolism

Substances

  • Bacterial Proteins
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Luminescent Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • yellow fluorescent protein, Bacteria
  • CDC20 protein, human
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • Endopeptidases