Cyclin-dependent kinase 9 or CDK9 is a
cyclin-dependent kinase associated with
P-TEFb
The positive transcription elongation factor, P-TEFb, is a multiprotein complex that plays an essential role in the regulation of transcription by RNA polymerase II (Pol II) in eukaryotes. Immediately following initiation Pol II becomes trapped in ...
.
Function
The protein encoded by this gene is a member of the
cyclin-dependent kinase (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
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
domain of the largest subunit of
RNA polymerase II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukary ...
. 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
TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene.
Function
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, an ...
, 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
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ...
with:
*
Androgen receptor,
*
CDC34[ and
* CCNK,]
* CCNT1,
* CCNT2,
* MYBL2,[
* ]RELA
Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the ''RELA'' gene.
RELA, also known as p65, is a REL-associated protein involved in NF-κB heterodimer formation, nuclear tran ...
,
* RB1,
* SKP1A.[
* ]SUPT5H
Transcription elongation factor SPT5 is a protein that in humans is encoded by the ''SUPT5H'' gene.
Interactions
SUPT5H has been shown to interact with:
* CDK9,
* Cyclin-dependent kinase 7,
* HTATSF1,
* PIN1,
* POLR2A,
* PRMT1 and ...
,[ and
* RNAP II.]
References
Further reading
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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