P40SDB25, a putative CDK inhibitor, has a role in the M/G1 transition in Saccharomyces cerevisiae.
The Saccharomyces cerevisiae protein kinase Dbf2 carries out an essential function in late mitosis, and its kinase activity is cell-cycle regulated around anaphase/telophase. We have isolated SDB25, a high copy suppressor of temperature-sensitive dbf2 mutants, and genetic analysis suggests that the two proteins may function in parallel pathways in late mitosis. SDB25 encodes p40, a previously characterized substrate and potent inhibitor of Cdc28 kinase activity. Sdb25 is a phosphoprotein, and Sdb25 immunoprecipitates have a histone H1 kinase activity that is CDC28-dependent. Remarkably, Sdb25 transcript levels, protein levels, and associated kinase activity are precisely cell-cycle regulated, sharing a common peak in late mitosis. Moreover, Sdb25 protein levels and associated kinase activity are sharply up-regulated at the peak of Dbf2 kinase activity in cells released from a dbf2 ts block. The Sdb25 protein then disappears around Start in the next cell cycle. This indicates that SDB25 function is confined to M/G1, and morphological analysis of sdb25 delta cells supports this conclusion. Our data suggest that Sdb25 functions in a pathway in late mitosis leading to the down-regulation of Cdc28 kinase activity as cells traverse the M/G1 boundary.
Laboratory of Yeast Genetics, National Institute for Medical Research, Mill Hill, London, UK.
J D
JD
Donovan
J H
JH
Toyn
A L
AL
Johnson
L H
LH
Johnston
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D017489:CDC28 Protein Kinase, S cerevisiae / Q000037:antagonists & inhibitors*; D002453:Cell Cycle / Q000235:genetics; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D004271:DNA, Fungal / Q000032:analysis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D016153:Genes, Suppressor; D005838:Genotype; D008938:Mitosis; D008969:Molecular Sequence Data; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012331:RNA, Fungal / Q000032:analysis; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic
D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D010750:Phosphoproteins; D012331:RNA, Fungal; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017489:CDC28 Protein Kinase, S cerevisiae