Cyclin-dependent kinase 9 or CDK9 is a
cyclin-dependent kinase
Cyclin-dependent kinases (CDKs) are a predominant group of serine/threonine protein kinases involved in the regulation of the cell cycle and its progression, ensuring the integrity and functionality of cellular machinery. These regulatory enzym ...
associated with
P-TEFb.
Function
The protein encoded by this gene is a member of the
cyclin-dependent kinase
Cyclin-dependent kinases (CDKs) are a predominant group of serine/threonine protein kinases involved in the regulation of the cell cycle and its progression, ensuring the integrity and functionality of cellular machinery. These regulatory enzym ...
(CDK) family. CDK family members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and known as important cell cycle regulators. This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the
C-terminal domain of the largest subunit of
RNA polymerase II
RNA polymerase II (RNAP II and Pol II) is a Protein complex, multiprotein complex that Transcription (biology), transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNA pol ...
. This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with this protein and cyclin T, which suggested a possible involvement of this protein in AIDS.
CDK9 is also known to associate with other proteins such as
TRAF2, and be involved in differentiation of skeletal muscle.
Inhibitors
Based on molecular docking results, Ligands-3, 5, 14, and 16 were screened among 17 different Pyrrolone-fused benzosuberene compounds as potent and specific inhibitors without any cross-reactivity against different CDK isoforms. Analysis of MD simulations and MM-PBSA studies, revealed the binding energy profiles of all the selected complexes. Selected ligands performed better than the experimental drug candidate (Roscovitine). Ligands-5 and 16 show specificity for CDK9. These ligands are expected to possess lower risk of side effects due to their natural origin.
Interactions
CDK9 has been shown to
interact with:
*
Androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...
,
*
CDC34[ and
* CCNK,]MYBL2
Myb-related protein B is a protein that in humans is encoded by the ''MYBL2'' gene.
Function
The protein encoded by this gene, a member of the MYB family of transcription factor genes, is a nuclear protein involved in cell cycle progression. ...
,[
* RELA,][
* SUPT5H,][ and
* RNAP II.]
References
Further reading
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See also
* Enitociclib
External links
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''Drosophila'' ''Cyclin dependent kinase 9'' - The Interactive Fly
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Cell cycle
Proteins
EC 2.7.11
{{2.7-enzyme-stub