Mcs2 and a novel CAK subunit Pmh1 associate with Skp1 in fission yeast.
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.
Bamps
Sophie
S
Laboratoire de Génétique Moléculaire (GEMO), University of Namur (FUNDP), 61 rue de Bruxelles, 5000 Namur, Belgium.
Westerling
Thomas
T
Pihlak
Arno
A
Tafforeau
Lionel
L
Vandenhaute
Jean
J
Mäkelä
Tomi P
TP
Hermand
Damien
D
D000595:Amino Acid Sequence; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D004718:Saccharomycetales / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D016213:Cyclins; C495066:Mcs2 protein, S pombe; D021122:Protein Subunits; D011994:Recombinant Proteins; D044786:S-Phase Kinase-Associated Proteins; D029702:Schizosaccharomyces pombe Proteins; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase