View source for Kinase Subfamily CDK20

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[[kinase classification|Kinase Classification]]: [[Kinase_Group_CMGC|Group CMGC]]: [[Kinase_Family_CDK|Family CDK]]: [[Kinase_Subfamily_CDK20|Subfamily CDK20]]

====CDK20 (CCRK)====
CDK20 is a cyclin-associated kinase that likely activates CDK2 or other CDKs, and RCK family kinases, and has an emerging role in cilium biology and possibly hedgehog signaling. Also known as CCRK ('''C'''ell '''C'''ycle '''R'''egulated '''K'''inase), CDK20 is most similar to CDK7 in sequence. Like CDK7, it has been reported to be a CDK-activating kinase (CAK) <cite>Liu, An</cite>, though this is disputed <cite>Wohlbold</cite>, and it is also reported to interact with cyclin H <cite>Qui</cite>. Its cyclin-binding motif (PNQALRE) is relatively well conserved, though distinct from that of CDK7 (NRTLARE), the better-known partner of cyclin H.

====Domain Structure====
Most CDK20 have a kinase domain flanked by short non-domain regions. The activation loop conserves a T/S that is the major phosphorylation site of CDK kinases (T160 in CDK2) but has not been seen to be phosphorylated.

====Evolutionary Range====
A single CDK20 gene is found in all animals, including CDK20/CCRK in mammals, dyf-18 in C.elegans and CG6800 in Drosophila. Scattered homologs exist in several protists, including chytrid fungi and some basidiomycetes, 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 <cite>Li, Avidor</cite> (nematodes have lost motile cilia, but have a divergent CDK20 homolog).

====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  [[Kinase_Subfamily_MOK|MOK]] subfamily kinase <cite>Asleson</cite>. Separately human CDK20 was shown to phosphorylate the MOK kinase ICK (CILK1 in human cells <cite>Fu</cite>, correlating with the Chlamydomonas finding that LF2 was epistatic to LF4 in a flagellar regrowth phenotype. C. elegans CDK20, dyf-18 was shown to be a transcriptional target of the RFX (daf-19) cilium master transcription factor <cite>Phirke</cite>. dyf-18 and the dyf-5/M04C9.5, a [[Kinase_Subfamily_MAK|MAK]], are both implicated in control of cilium length and branching in nematode neurons, are supporessors of the kif17 kinesin, and are localized at the distal end of sensory cilia <cite>Yi, Maurya </cite>

Another report shows human CDK20 to be stabilized by binding to the Bromi (TBC1D32) 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 <cite>Ko</cite>. 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. Bromi and another interacting protein, FAM149B1, are both conserved across animals and found in chytrids, oomycetes, and scattered other basal organisms, in a pattern similar to that of CDK20, suggesting that their interaction, or association with cilia, is ancient.

====Disease Association====
Human CDK20 has been implicated in several forms of cancer by its overexpression and RNAi phenotypes <cite>An, Wu, Ng</cite>. A cardiac-selective splice isoform has been implicated in heart failure and to promote growth and survival <cite>Qiu</cite>. 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).


[[User:Gerard|Gerard]] 12:06, 21 July 2011 (PDT)
[[User:Gerard|Gerard]] 15:01, 15 December 2022 (PDT)

===References===
<biblio>
#An pmid=20466538
#Asleson pmid=9504917
#Avidor pmid=15137945
#Fu pmid=16954377
#Ko pmid=20159594
#Li pmid=15137946
#Liu pmid=14597612
#Yi pmid=29655266
#Maurya pmid=30955935
#Ng pmid=17565152
#Phirke pmid=21740898
#Qui pmid=18508765
#Tam pmid=17353359
#Wohlbold pmid=16552187
#Wu pmid=19672860
</biblio>