Kinase Subfamily CDK20

From WikiKinome

Kinase Classification: Group CMGC: Family CDK

CDK20 (CCRK)

CDK20 is a cyclin-associated kinase that likely activates CDK2 or other CDKs, and has an emerging role in cilium biology and possibly hedgehog signaling. Also known as CCRK (Cell Cycle Regulated Kinase), CDK20 is most similar to CDK7 in sequence. Like CDK7, it has been reported to be a CDK-activating kinase (CAK) Liu, An, though this is disputed Wohlbold, and it is also reported to interact with cyclin H Qui. Its cyclin-binding motif (PNQALRE) is relatively well conserved, though distinct from that of CDK7 (NRTLARE), the better-known partner of cyclin H.

Evolutionary Range

A single CDK20 gene is found in all animals. Scattered homologs exist in several protists, including a chytrid fungus, Phytophthora, and the alga Chlamydomonas, but not higher plants. This pattern is similar to that of many other cilium-related genes, and correlates to the loss of all cilia in Dictyostelium, higher plants and non-chytrid fungi Li, Avidor (nematodes have lost motile cilia, but have a divergent CDK20 homolog).

Disease Association

Human CDK20 has been implicated in several forms of cancer by its overexpression and RNAi phenotypes An, Wu, Ng. A cardiac-selective splice isoform has been implicated in heart failure and to promote growth and survival Qiu. These experiments also show a consistent phenotype implicating CDK20 in the G1-to-S phase transition in cell cycle of the cancer cells examined. In hepatocellular carcinoma, CDK20 expression correlates with tumor progression, expression is induced by androgen receptor, and participates in Wnt pathway signaling to drive proliferation (Feng, PMID=21747169).

CDK20 function and cilia

Multiple lines of evidence also point to a role for CDK20 in flagellum biosynthesis: Mutants in Chlamydomonas CDK20 (called LF2 - long flagella 2) disrupt flagellum length control and assembly. LF2 interacts genetically with LF4, which encodes a MOK subfamily kinase Asleson. Separately human CDK20 was shown to phosphorylate the MOK kinase ICK in human cells Fu, correlating with the Chlamydomonas finding that LF2 was epistatic to LF4 in a flagellar regrowth phenotype. C. elegans CCRK was shown to be a transcriptional target of the RFX (daf-19) cilium master transcription factor Phirke.

Another report shows human CDK20 to be stabilized by binding to the Bromi protein. Bromi is poorly understood, but seems to link the axoneme of the flagellum to the plasma membrane. Bromi effects the localization of Gli2 in the flagellum and so influences hedgehog signaling Ko. Curiously, antibody staining by the protein atlas (http://proteinatlas.org) shows Bromi specifically in the mitochondrion, while CDK20 is found in the nucleus and the mitochondrion.

Gerard 12:06, 21 July 2011 (PDT)

References

<biblio>

1. An pmid=20466538
2. Asleson pmid=9504917
3. Avidor pmid=15137945
4. Fu pmid=16954377
5. Ko pmid=20159594
6. Li pmid=15137946
7. Liu pmid=14597612
8. Ng pmid=17565152
9. Phirke pmid=21740898
10. Qui pmid=18508765
11. Tam pmid=17353359
12. Wohlbold pmid=16552187
13. Wu pmid=19672860

</biblio>