Fission yeast Clp1p phosphatase regulates G2/M transition and coordination of cytokinesis with cell cycle progression

Curr Biol. 2001 Jun 26;11(12):931-40. doi: 10.1016/s0960-9822(01)00268-8.

Abstract

Background: In Saccharomyces cerevisiae the mitotic-exit network (MEN) functions in anaphase to promote the release of the Cdc14p phosphatase from the nucleolus. This release causes mitotic exit via inactivation of the cyclin-dependent kinase (Cdk). Cdc14p-like proteins are highly conserved; however, it is unclear if these proteins regulate mitotic exit as in S. cerevisiae. In Schizosaccharomyces pombe a signaling pathway homologous to the MEN and termed the septation initiation network (SIN) is required not for mitotic exit, but for initiation of cytokinesis and for a cytokinesis checkpoint that inhibits further cell cycle progression until cytokinesis is complete.

Results: We have identified the S. pombe Cdc14p homolog, Clp1p, and show that it is not required for mitotic exit but rather functions together with the SIN in coordinating cytokinesis with the nuclear-division cycle. As cells enter mitosis, Clp1p relocalizes from the nucleolus to the spindle and site of cell division. Clp1p exit from the nucleolus does not depend on the SIN, but the SIN is required for keeping Clp1p out of the nucleolus until completion of cytokinesis. Clp1p, in turn, may promote the activation of the SIN by antagonizing Cdk activity until cytokinesis is complete and thus ensuring that cytokinesis is completed prior to the initiation of the next cell cycle. In addition to its roles in anaphase, Clp1p regulates the G2/M transition since cells deleted for clp1 enter mitosis precociously and cells overexpressing Clp1p delay mitotic entry. Unlike Cdc14p, Clp1p appears to antagonize Cdk activity by preventing dephosphorylation of Cdc2p on tyrosine.

Conclusions: S. pombe Clp1p affects cell cycle progression in a markedly different manner than its S. cerevisiae homolog, Cdc14p. This finding raises the possibility that related phosphatases in animal cells will prove to have important roles in coordinating the onset of cytokinesis with the events of mitosis.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division / genetics
  • Cell Division / physiology*
  • Cell Line
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Genes, Reporter
  • Microscopy, Fluorescence
  • Nuclear Proteins*
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Tyrosine Phosphatases*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / physiology*
  • Schizosaccharomyces pombe Proteins*

Substances

  • Cell Cycle Proteins
  • Fungal Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Schizosaccharomyces pombe Proteins
  • wee1 protein, S pombe
  • Protein-Tyrosine Kinases
  • Phosphoprotein Phosphatases
  • Clp1 protein, S. pombe
  • Protein Tyrosine Phosphatases