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 eukaryo ...
. 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
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with:
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Androgen receptor,
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CDC34
''CDC34'' is a gene that in humans encodes the protein Ubiquitin-conjugating enzyme E2 R1. This protein is a member of the ubiquitin-conjugating enzyme family, which catalyzes the covalent attachment of ubiquitin to other proteins.
CDC34 was orig ...
[ 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. T ...
,[
* ]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 tra ...
,SKP1A
S-phase kinase-associated protein 1 is an enzyme that in humans is encoded by the ''SKP1'' gene.
This gene encodes a protein that is a member of the SCF ubiquitin ligase protein complex. It binds to F-box proteins (proteins containing an F-box ...
.[
* SUPT5H,][ and
* ]RNAP 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 eukaryo ...
.
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