CDC28/YBR160W Summary Help

Standard Name CDC28 1, 2
Systematic Name YBR160W
Alias CDK1 , HSL5 , SRM5
Feature Type ORF, Verified
Description Cyclin-dependent kinase (CDK) catalytic subunit; master regulator of mitotic and meiotic cell cycles; alternately associates with G1 (CLNs), S and G2/M (CLBs) phase cyclins, which provide substrate specificity; regulates cell cycle and basal transcription, chromosome duplication and segregation, lipid biosynthesis, membrane trafficking, polarized growth, and morphogenesis; abundance increases in DNA replication stress; transcript induction in osmostress involves antisense RNA (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and see Summary Paragraph)
Name Description Cell Division Cycle 16
Chromosomal Location
ChrII:560078 to 560974 | ORF Map | GBrowse
Genetic position: 90 cM
Gene Ontology Annotations All CDC28 GO evidence and references
  View Computational GO annotations for CDC28
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Classical genetics
reduction of function
Large-scale survey
reduction of function
1023 total interaction(s) for 566 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 70
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 53
  • Biochemical Activity: 396
  • Co-localization: 4
  • Co-purification: 8
  • PCA: 46
  • Protein-peptide: 2
  • Reconstituted Complex: 26
  • Two-hybrid: 36

Genetic Interactions
  • Dosage Growth Defect: 6
  • Dosage Lethality: 3
  • Dosage Rescue: 25
  • Negative Genetic: 41
  • Phenotypic Enhancement: 54
  • Phenotypic Suppression: 18
  • Positive Genetic: 5
  • Synthetic Growth Defect: 162
  • Synthetic Lethality: 37
  • Synthetic Rescue: 30

Expression Summary
Length (a.a.) 298
Molecular Weight (Da) 34,061
Isoelectric Point (pI) 8.5
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrII:560078 to 560974 | ORF Map | GBrowse
Genetic position: 90 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..897 560078..560974 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000364

Cdc28 is the catalytic subunit of the main cell cycle cyclin-dependent kinase (CDK) (17, 4). Homologs include CDK1 in animals and cdc2 in S. pombe. Waves of CDK activity drive events of the cell cycle through phosphorylation of key substrates (18, 19 and reviewed in 11). To accomplish these waves of activity, Cdc28p associates with different regulators throughout the cell cycle (20). The expression of several of these regulators is periodic which serves to limit their window of action to the proper time in the cell cycle (21, 22, 23, 24, 25, 26).

The first wave of CDK activity occurs when Cdc28p associates with G1 cyclins and Cks1p (27). The G1 cyclins are Cln1p, Cln2p, and Cln3p. Cln3p/Cdc28p activity is required for setting the size threshold at which cells pass through START (commitment to duplication and division) (28). Once committed Cln3p/Cdc28p inactivates a repressor of G1 transcription, Whi5p, which in turn leads to active SBF (Swi4p-Swi6p) and MBF (Mbp1p-Swi6p), transcription factors that promote transcription of CLN1, CLN2, and genes required for S-phase (29, 30, 31). Cln1p and Cln2p are important for initiating polarized growth at the site of bud emergence, promoting spindle pole body (SPB) duplication and inhibiting Sic1p and Cdh1p, two CDK inhibitors (32, 33). During G1, Sic1p binds and inhibits the growing pool of Cdc28p/B-type cyclin complexes. Towards the end of G1, Cdc28p/Cln1p and Cdc28p/Cln2p complexes phosphorylate Sic1p and target it for degradation. (34, 35). The absence of Sic1p allows a wave of CDK/B-cyclin activity that drives DNA replication and entry into mitosis (36).

B-type cyclins Clb1p, Clb2p, Clb3p, Clb4p, Clb5p, and Clb6p regulate Cdc28p during S, G2, and M phases. Cdc28p association with Clb5p and Clb6p drives DNA replication (37). Association with Clb3p, Clb4p, and Clb5p promotes maturation and separation of spindle pole bodies, and proper spindle segregation (38, 39, 40) while Cdc28p association with Clb2p (and to some extent Clb1p, Clb3p, and Clb4p) promotes entry into mitosis and triggers a switch in bud growth from polarized to isotropic (32, 41). The metaphase to anaphase transition occurs when securin (Pds1p), an inhibitor of DNA segregation is destroyed by the proteosome. Mitotic CDK activity is required to target Pds1p for degradation by directly phosphorylating Pds1p and activating the Anaphase Promoting Complex/Cyclosome (APC/C). (42, 43, 44).

Once DNA is segregated, exit from mitosis (spindle disassembly, cytokinesis and transition to the next G1) requires that mitotic CDK activity be turned off (45). This is accomplished by degradation of mitotic cyclins and inhibition of remaining mitotic activity by Sic1p. In the absence of mitotic CDK activity, G1 cyclins can once again accumulate (46, 43).

In addition to being regulated by binding partners, Cdc28p is regulated by post-translational modifications. Cak1p phosphorylation of Cdc28p on threonine 169 is essential for CDK activity and is thought to precede cyclin binding (47). Phosphorylation of Cdc28p on tyrosine 19 (Y19) by Swe1p kinase (wee1 in S. pombe) inhibits mitotic CDK activity and hence, entry into mitosis (48, 49, 50, 51, 52). This phosphorylation is removed by the phosphatase Mih1p (homolog of cdc25 in S. pombe) (53). Phosphorylation of Y19 is critical for enforcing the morphogenesis checkpoint. When cells experience an environmental perturbation that disrupts bud formation, the morphogenesis checkpoint delays entry into mitosis until a bud is formed. The checkpoint impinges on Swe1p and Mih1p to inactivate the mitotic CDK, insuring that mitosis does not occur in an unbudded cell (54, 55). Unlike in S. pombe and metazoans, Swe1p and/or Mih1p are not direct targets of the spindle checkpoints (56) or DNA checkpoints (57).

Developmental programs such as mating, meiosis and sporulation, and pseudohyphal growth require alterations in cell cycle control. For example, during mating, pheromone-dependent inhibition of Cln/Cdc28p complexes by Far1p arrests cells in G1 so cell-cell fusion can occur. When sporulation is induced, cells enter meiosis from G1, but CLN1 and CLN2 are repressed by a mechanism that makes meiosis and mitosis incompatible (58).

Last updated: 2006-08-09 Contact SGD

References cited on this page View Complete Literature Guide for CDC28
1) Nasmyth KA and Reed SI  (1980) Isolation of genes by complementation in yeast: molecular cloning of a cell-cycle gene. Proc Natl Acad Sci U S A 77(4):2119-23
2) Hartwell LH, et al.  (1973) Genetic Control of the Cell Division Cycle in Yeast: V. Genetic Analysis of cdc Mutants. Genetics 74(2):267-286
3) Reed SI  (1980) The selection of S. cerevisiae mutants defective in the start event of cell division. Genetics 95(3):561-77
4) Mendenhall MD and Hodge AE  (1998) Regulation of Cdc28 cyclin-dependent protein kinase activity during the cell cycle of the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev 62(4):1191-243
5) Reed SI and Wittenberg C  (1990) Mitotic role for the Cdc28 protein kinase of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 87(15):5697-701
6) Wittenberg C, et al.  (1990) G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase. Cell 62(2):225-37
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51) Hu F and Aparicio OM  (2005) Swe1 regulation and transcriptional control restrict the activity of mitotic cyclins toward replication proteins in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 102(25):8910-5
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