Mcs2 and a novel CAK subunit Pmh1 associate with Skp1 in fission yeast

Biochem Biophys Res Commun. 2004 Dec 24;325(4):1424-32. doi: 10.1016/j.bbrc.2004.10.190.

Abstract

The Mcs6 CDK together with its cognate cyclin Mcs2 represents the CDK-activating kinase (CAK) of fission yeast Cdc2. We have attempted to determine complexes in which Mcs6 and Mcs2 mediate this and possible other functions. Here we characterize a novel interaction between Mcs2 and Skp1, a component of the SCF (Skp1-Cullin-F box protein) ubiquitin ligase. Furthermore, we identify a novel protein termed Pmh1 through its association with Skp1. Pmh1 associates with the Mcs6-Mcs2 complex, enhancing its kinase activity, and represents the apparent homolog of metazoan Mat1. Association of Mcs2 or Pmh1 with Skp1 does not appear to be involved in proteolytic degradation, as these complexes do not contain Pcu1, and levels of Mcs2 or Pmh1 are not sensitive to inhibition of SCF and the 26S proteasome. The identified interactions between Skp1 and two regulatory CAK subunits may reflect a novel mechanism to modulate activity and specificity of the Mcs6 kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Cyclins / genetics
  • Cyclins / metabolism*
  • Molecular Sequence Data
  • Protein Subunits
  • Recombinant Proteins / metabolism
  • S-Phase Kinase-Associated Proteins / genetics
  • S-Phase Kinase-Associated Proteins / metabolism*
  • Saccharomycetales / genetics
  • Saccharomycetales / metabolism*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship

Substances

  • Cyclins
  • Mcs2 protein, S pombe
  • Protein Subunits
  • Recombinant Proteins
  • S-Phase Kinase-Associated Proteins
  • Schizosaccharomyces pombe Proteins
  • Cyclin-Dependent Kinases
  • cyclin-dependent kinase-activating kinase