The role of proteolysis in cell cycle progression in Schizosaccharomyces pombe

H Yamano1, J Gannon, T Hunt

  • 1ICRF Clare Hall Laboratories, South Mimms, Herts, UK.

The EMBO Journal
|October 1, 1996
PubMed

Insights

The destruction of Cdc13 (a B-type cyclin) is essential for mitotic exit in Schizosaccharomyces pombe. Its destruction box, RHALDDVSN, is key for this process and for regulating cell cycle progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • B-type cyclins are crucial regulators of the cell cycle.
  • Proteolysis of cyclins, particularly via the destruction box motif, controls cell cycle transitions.
  • Understanding cyclin degradation is key to understanding cell cycle control.

Purpose of the Study:

  • To identify the destruction box of the Schizosaccharomyces pombe B-type cyclin, Cdc13.
  • To investigate the role of Cdc13 destruction in mitotic exit and cell cycle progression.
  • To explore the proteolytic machinery involved in cyclin degradation.

Main Methods:

  • Utilized a cell-free system derived from Xenopus eggs.
  • Expressed modified Cdc13 proteins in Schizosaccharomyces pombe.
  • Analyzed the effects of indestructible Cdc13 and N-terminal fragments on cell cycle progression.

Main Results:

  • Identified residues 59-67 (RHALDDVSN) as the destruction box of Cdc13.
  • Indestructible Cdc13 blocked cells in anaphase and inhibited septation, indicating its destruction is necessary for mitotic exit.
  • A competitive inhibitor of destruction box-mediated proteolysis inhibited both sister chromatid separation and Cdc13 destruction.
  • Expression of a Cdc13 fragment overcame G1 arrest in cdc10 mutants, suggesting shared proteolytic machinery.

Conclusions:

  • Cdc13 destruction is a critical requirement for exit from mitosis in S. pombe.
  • The identified destruction box is essential for regulating Cdc13 proteolysis and cell cycle progression.
  • The same proteolytic machinery degrades Cdc13 and proteins required for S phase initiation.

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