Cdk10 is a member of the Cdc2 kinase family and is involved in the regulation of the G2/M phase of the cell cycle. Cdk10 was originally identified based on its homology to Cdc2 and shares common features of cyclin-dependent kinases (Cdks). These include the XI conserved region of the protein kinase and the PSTAIRE-like sequence PISSLRE. Cdk10 also contains amino acids that are important regulatory sites in Cdc2 and other Cdks. These include tyrosine and threonine sites in the ATP-binding domain, and conserved threonine corresponding to threonine 161 of Cdc2. The phosphorylation status of these sites is critical for determining Cdks activity, suggesting that Cdk10 is under similar regulation.
Introductions
In addition to being regulated by phosphorylation of key residues, Cdk activity is also regulated by binding to important associate proteins. Cdks remain inactive unless they are associated with their cyclin chaperones. Overexpression of kinase-inactivated Cdks (also known as dominant negative mutants) functionally inactivates their wild-type counterparts through competition-requiring interacting proteins, especially cyclin chaperones. These mutant kinases contain a point mutation at a key aspartic acid in the ATPase domain, thereby enzymatically inactivating the kinase, but maintaining the appropriate structural conformation, so they can bind their normal protein chaperones. This results in the functional inactivation of endogenous wild-type Cdk and may stop the cell cycle process at the time position where a particular Cdk is active. For example, overexpression of dominant negative Cdc2 arrests G2/M cells, while dominant negative Cdk2 arrests cells during the G1 phase of the cell cycle, and these blocks can be rescued by appropriate expression of cyclin.
Functions
The protein encoded by this gene belongs to the CDK subfamily of the Ser/Thr protein kinase family. The members of the CDK subfamily are highly similar to the gene products of Saccharomyces cerevisiae cdc28 and Schizosaccharomyces cerevisiae cdc2 and are known to be essential for cell cycle progression. This kinase has been shown to play a role in cell proliferation. Its function is limited to the G2-M phase of the cell cycle. At least three alternative splicing transcription variants encoding different isoforms have been reported, two of which contain multiple non-AUG translation initiation sites.
Protein association of CDK10
The protein association of Cdk10 may also be important for its function in cells. Overexpression of the kinase-inactivated Cdk10 arrests cells in the G2/M phase of the cell cycle and results in growth inhibition of U20S cells, similar to that observed for other Cdks involved in the cell cycle. However, no cyclin chaperone has been identified for this Cdk, and no other protein has been characterized for binding to Cdk10. Therefore, the identification of proteins associated with Cdk10 is of great interest, as they may prove to be regulated or regulated by Cdk10. We performed an interaction trap or two-hybrid screen in Saccharomyces cerevisiae to identify proteins associated with Cdk10 to help us understand this putative kinase. In this study, we reported that Cdk10 binds to Ets2 transcription factor in vitro and in vivo. This interaction occurs through the N-terminus of Ets2, which contains Ets2's transactivation domain and a highly conserved pointing (PNT) domain. The interaction of PNT domain and protein is involved, and we found that Cdk10 requires a complete PNT domain to bind Ets2. However, Cdk10 cannot recognize the highly similar amino terminus of Ets1. In addition to interacting in vitro and in vivo, we found that Cdk10 inhibits Ets2 transactivation in mammalian cells.
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