Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.
Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.
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 domain of the largest subunit of RNA polymerase II. 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. [5]
CDK9 is also known to associate with other proteins such as TRAF2, and be involved in differentiation of skeletal muscle. [6]
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. [7]
CDK9 has been shown to interact with:
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 in eukaryotes. Immediately following initiation Pol II becomes trapped in promoter proximal paused positions on the majority of human genes. P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (DSIF) and negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol II and this causes the transition into productive elongation leading to the synthesis of mRNAs. P-TEFb is regulated in part by a reversible association with the 7SK snRNP. Treatment of cells with the P-TEFb inhibitors DRB or flavopidirol leads to loss of mRNA production and ultimately cell death.
In molecular biology 7SK is an abundant small nuclear RNA found in metazoans. It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb. 7SK is found in a small nuclear ribonucleoprotein complex (snRNP) with a number of other proteins that regulate the stability and function of the complex.
DNA-directed RNA polymerase II subunit RPB1, also known as RPB1, is an enzyme that is encoded by the POLR2A gene in humans.
Cyclin-T1 is a protein that in humans is encoded by the CCNT1 gene.
DNA-directed RNA polymerase II subunit RPB7 is an enzyme that in humans is encoded by the POLR2G gene.
DNA-directed RNA polymerases I, II, and III subunit RPABC3 is a protein that in humans is encoded by the POLR2H gene.
DNA-directed RNA polymerases I, II, and III subunit RPABC5 is a protein that in humans is encoded by the POLR2L gene.
DNA-directed RNA polymerase II subunit RPB4 is an enzyme that in humans is encoded by the POLR2D gene.
CDK-activating kinase assembly factor MAT1 is an enzyme that in humans is encoded by the MNAT1 gene.
Transcription elongation factor SPT5 is a protein that in humans is encoded by the SUPT5H gene.
Cyclin-H is a protein that in humans is encoded by the CCNH gene.
General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.
HIV Tat-specific factor 1 is a protein that in humans is encoded by the HTATSF1 gene.
Protein HEXIM1 is a protein that in humans is encoded by the HEXIM1 gene.
Cyclin-T2 is a protein that in humans is encoded by the CCNT2 gene.
General transcription factor IIH subunit 1 is a protein that in humans is encoded by the GTF2H1 gene.
CTD small phosphatase-like protein is an enzyme that in humans is encoded by the CTDSPL gene.
Cyclin-K is a protein that in humans is encoded by the CCNK gene.
Protein HEXIM2 is a protein that in humans is encoded by the HEXIM2 gene.
In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.
