The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae

Curr Biol. 1998 Apr 23;8(9):497-507. doi: 10.1016/s0960-9822(98)70201-5.

Abstract

Background: Following chromosome segregation in anaphase, ubiquitin-dependent degradation of mitotic cyclins contributes to the exit from mitosis. A key step in this process is catalyzed by a ubiquitin-protein ligase known as the anaphase-promoting complex (APC), the regulation of which is poorly understood. The Polo-related protein kinase Cdc5 in Saccharomyces cerevisiae might encode a regulator of the APC, because cdc5 mutant cells arrest with a late mitotic phenotype similar to that observed in cells with defective cyclin destruction.

Results: We investigated the role of Cdc5 in the regulation of mitotic cyclin degradation. In cdc5-1 mutant cells, we observed a defect in the destruction of cyclins and a reduction in the cyclin-ubiquitin ligase activity of the APC. Overexpression of CDC5 resulted in increased APC activity and mitotic cyclin destruction in asynchronous cells or in cells arrested in metaphase. CDC5 mutation or overexpression did not affect the degradation of the APC substrate Pds 1, which is normally degraded at the metaphase-to-anaphase transition. Cyclin-specific APC activity in cells overexpressing CDC5 was reduced in the absence of the APC regulatory proteins Hct 1 and Cdc20. In G1, Cdc5 itself was degraded by an APC-dependent and Hct1-dependent mechanism.

Conclusions: We conclude that Cdc5 is a positive regulator of cyclin-specific APC activity in late mitosis. Degradation of Cdc5 in G1 might provide a feedback mechanism by which the APC destroys its activator at the onset of the next cell cycle.

Publication types

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

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • CDC28 Protein Kinase, S cerevisiae / physiology
  • Cdc20 Proteins
  • Cdh1 Proteins
  • Cell Cycle Proteins / physiology
  • Cyclin B*
  • Cyclins / metabolism*
  • Cyclins / physiology
  • Cytoskeletal Proteins / physiology
  • Fungal Proteins / metabolism
  • Fungal Proteins / physiology*
  • G1 Phase / physiology
  • Mutation / genetics
  • Mutation / physiology
  • Nuclear Proteins / physiology
  • Protein Kinases / biosynthesis
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Securin
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology*

Substances

  • Adenomatous Polyposis Coli Protein
  • CDC20 protein, S cerevisiae
  • CDH1 protein, S cerevisiae
  • CLB2 protein, S cerevisiae
  • Cdc20 Proteins
  • Cdh1 Proteins
  • Cell Cycle Proteins
  • Cyclin B
  • Cyclins
  • Cytoskeletal Proteins
  • Fungal Proteins
  • Nuclear Proteins
  • PDS1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Securin
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • CDC5 protein, S cerevisiae
  • CDC28 Protein Kinase, S cerevisiae