The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDKs) through conformational changes.[4][5] Activation of CDKs through their cyclin partner, creates kinase complexes that will activate target proteins through phosphorylation. Targeted proteins can then ultimately regulate decisions of a cell’s progression within the cell cycle to occur. This gene product may be seen to play a dual role in both regulating CDK and RNA polymerase II (RNAP2) activities.[3] Cyclin K only uses RNA recruitment to activate transcription.[6]
Interactions
Cyclin K has been shown to interact with multiple CDKs including CDK9 and latest CDK12 and CDK13.[2][5] Roles include helping to phosphorylate C-terminal domains of subunits of RNAP2.[7] Cyclin K is most noted for its associated induction of processive elongation.[4] Also, identified with G1 and S phase cyclin activity, however functions are not deeply understood.[1][8]
Cyclin K also interacts with HIV nef protein.[9] In the presence of overexpressed Nef protein, Cyclin k and CDK9 binding is induced, inhibiting the positive elongation factor of other CDK9 binding complexes, resulting in an inhibition of specific HIV-1 gene expression.[5][9] CDK 13 may also be characterized to interact with HIV mRNA splicing, alongside Nef, and the underexpression of Gag and Env related proteins. [8][6]
Cyclin K is indispensable for Leukemia growth. SETD1A, is also known to bind Cyclin K through its FLOS domain.[10] The interaction is shown to be important to DNA damage response genes and for Leukemia proliferation.[6][10]
↑ 2.02.1Fu TJ, Peng J, Lee G, Price DH, Flores O (December 1999). "Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription". The Journal of Biological Chemistry. 274 (49): 34527–30. doi:10.1074/jbc.274.49.34527. PMID10574912.
↑ 10.010.1Hoshii T, Cifani P, Feng Z, Huang CH, Koche R, Chen CW, Delaney CD, Lowe SW, Kentsis A, Armstrong SA (February 2018). "A Non-catalytic Function of SETD1A Regulates Cyclin K and the DNA Damage Response". Cell. 172 (5): 1007–1021.e17. doi:10.1016/j.cell.2018.01.032. PMID29474905.
Further reading
Lin X, Taube R, Fujinaga K, Peterlin BM (May 2002). "P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA". The Journal of Biological Chemistry. 277 (19): 16873–8. doi:10.1074/jbc.M200117200. PMID11884399.
Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID16713569.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID17081983.
