V. Measday et al., A FAMILY OF CYCLIN-LIKE PROTEINS THAT INTERACT WITH THE PHO85 CYCLIN-DEPENDENT KINASE, Molecular and cellular biology, 17(3), 1997, pp. 1212-1223
In budding yeast, entry into the mitotic cell cycle, or Start, require
s the Cdc28 cyclin-dependent kinase (Cdk) and one of its three associa
ted G(1) cyclins, Cln1, Cln2, or Cln3. In addition, two other G(1) cyc
lins, Pcl1 and Pcl2, associate with a second Cdk, Pho85, to contribute
to Start. Although Pho85 is not essential for viability, Pcl1,2-Pho85
kinase complexes become essential for Start in the absence of Cln1,2-
Cdc28 kinases. In addition, Pho85 interacts with a third cyclin, Pho80
, to regulate acid phosphatase gene expression. Other cellular roles f
or Pho85 cyclin-Cdk complexes are suggested by the multiple phenotypes
associated with deletion of PHO85, in addition to Start defects and d
eregulated acid phosphatase gene expression. Strains with pho80, pcl1,
and pcl2 deletions show only a subset of the pho85 mutant phenotypes,
suggesting the existence of additional Pho85 cyclins (Pcls). We used
two-hybrid screening and database searching to identify seven addition
al cyclin-related genes that may interact with Pho85. We found that al
l of the new genes encode proteins that interacted with Pho85 in an af
finity chromatography assay. One of these genes, CLG1, was previously
suggested to encode a cyclin, based on the protein's sequence homology
to Pcl1 and Pcl2. We have named the other genes PCL5, PCL6, PCL7, PCL
8, PCL9, and PCL10. On the basis of sequence similarities, the PCLs ca
n be divided into two subfamilies: the Pcl1,2-like subfamily and the P
ho80-like subfamily. We found that deletion of members of the Pcl1,2 c
lass of genes resulted in pronounced morphological abnormalities. In a
ddition, we found that expression of one member of the Pcl1,2 subfamil
y, PCL9, is cell cycle regulated and is decreased in cells arrested in
G(1) by pheromone treatment. Our studies suggest that Pho85 associate
s with multiple cyclins and that subsets of cyclins may direct Pho85 t
o perform distinct roles in cell growth and division.