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Cyclin-dependent kinase 9

TAK, CDK9, Cyclin-Dependent Kinase 9
The protein encoded by this gene is a member of the cyclin-dependent protein 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. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: PCNA, POLYMERASE, CAN, V1a, ACID
Papers using TAK antibodies
Identification of the vesicular nucleotide transporter (VNUT) in taste cells.
Meyerhof Wolfgang, In PLoS ONE, 2008
... Slices containing vallate taste buds were mounted on a glass coverslip coated with Cell-Tak (Becton Dickinson, Franklin Lakes, NJ, USA), ...
In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector
Fujinaga Koh et al., In Retrovirology, 1995
... Anti-myc, anti-HA, anti-CycT1, anti-Cdk9, and anti-Ub antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA) ...
Papers on TAK
Molecular principle of the cyclin-dependent kinase selectivity of 4-(thiazol-5-yl)-2-(phenylamino) pyrimidine-5-carbonitrile derivatives revealed by molecular modeling studies.
Hou et al., Suzhou, China. In Phys Chem Chem Phys, Feb 2016
4-(thiazol-5-yl)-2-(phenylamino) pyrimidine derivatives are effective inhibitors of CDKs, among which the most promising inhibitor 12u demonstrates high binding affinity to CDK9 and attenuated binding affinity to other homologous kinases, such as CDK2.
Overview of CDK9 as a Target in Cancer Research.
Giordano et al., Philadelphia, United States. In Cell Cycle, Feb 2016
UNASSIGNED: CDK9 is a protein in constant development in cancer therapy.
The Broad Spectrum Histone Deacetylase Inhibitors Vorinostat and Panobinostat Activate Latent HIV in CD4+ T cells in part through Phosphorylation of the T-Loop of the CDK9 Subunit of P-TEFb.
Rice et al., Houston, United States. In Aids Res Hum Retroviruses, Feb 2016
HIV provirus transcription depends critically on the positive transcription elongation factor b (P-TEFb), whose core components are cyclin-dependent kinase 9 (CDK9) and cyclin T1.
The phosphodiesterase 10A selective inhibitor TAK-063 improves cognitive functions associated with schizophrenia in rodent models.
Kimura et al., Takedamachi, Japan. In J Pharmacol Exp Ther, Jan 2016
TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one] is a potent and selective phosphodiesterase 10A inhibitor that produces antipsychotic-like effects in rodent models of schizophrenia.
RNA polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II.
Roeder et al., New York City, United States. In Science, Jan 2016
Paused Pol II release is thought to require the kinase activity of cyclin-dependent kinase 9 (CDK9) for the phosphorylation of DRB sensitivity-inducing factor, negative elongation factor, and C-terminal domain (CTD) serine-2 of Pol II.
GPR40 Agonists for the Treatment of Type 2 Diabetes Mellitus: Benefits and Challenges.
Mohammad, Riyadh, Saudi Arabia. In Curr Drug Targets, Jan 2016
GPR40 agonists TAK-875 and AMG 837 have reached clinical trials and TAK 875 was shown to improve glycemic control in Type 2 diabetic patients.
Increased cyclin T1 expression as a favorable prognostic factor in treating gastric adenocarcinoma.
Hsu et al., Taiwan. In Oncol Lett, Dec 2015
However, few studies have investigated the role of cyclin T1 and cyclin-dependent kinase 9 (CDK9) in gastric adenocarcinoma.
The Establishment of a Hyperactive Structure Allows the Tumour Suppressor Protein p53 to Function through P-TEFb during Limited CDK9 Kinase Inhibition.
Meisterernst et al., Münster, Germany. In Plos One, Dec 2015
CDK9 is the catalytic subunit of positive elongation factor b (P-TEFb) that controls the transition of RNA polymerase II (RNAPII) into elongation.
[New therapies in metastatic castration resistant prostate cancer].
Massard et al., Villejuif, France. In Bull Cancer, Jun 2015
Several other treatments are on trial targeting different pathways: androgene pathway (TAK-007, ARN-509, ODM-201, TOK-001), immune system (sipuleucel, ipilimumab, PROSTVAC-V/F, tasquinimod), but also tumor cell (PARP inhibitor, cabozantinib).
Endothelin receptors and their antagonists.
Davenport et al., Cambridge, United Kingdom. In Semin Nephrol, Mar 2015
The role of the two receptors has been delineated using highly selective ET(A) (BQ123, TAK-044) and ET(B) (BQ788) peptide antagonists.
Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors.
Coumar et al., Pondicherry, India. In Curr Cancer Drug Targets, 2014
The majority of the inhibitors (VX-680/MK-0457, PHA-739358, CYC116, SNS-314, AMG 900, AT-9283, SCH- 1473759, ABT-348, PF-03814735, R-763/AS-703569, KW-2449 and TAK-901) are pan-selective (isoform non-selective) and few are Aurora A (MLN8054, MLN8237, VX-689/MK5108 and ENMD 2076) and Aurora B (AZD1152 and GSK1070916) sub-type selective.
High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875.
Okada et al., San Diego, United States. In Nature, 2014
TAK-875, or fasiglifam, is an orally available, potent and selective partial agonist of hGPR40 receptor, which reached phase III clinical trials for the potential treatment of type-2 diabetes mellitus.
HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia.
Espinosa et al., Boulder, United States. In Cell, 2013
HIF1A induces binding of CDK8-Mediator and the super elongation complex (SEC), containing AFF4 and CDK9, to alleviate RNAPII pausing.
The super elongation complex (SEC) family in transcriptional control.
Shilatifard et al., Kansas City, United States. In Nat Rev Mol Cell Biol, 2012
Studies indicate that the super elongation complex (SEC) consisting of ELL, P-TEFb (CDK9) and MLL required for rapid transcriptional induction in the presence or absence of paused RNA polymerase II (Pol II).
Separate domains of fission yeast Cdk9 (P-TEFb) are required for capping enzyme recruitment and primed (Ser7-phosphorylated) Rpb1 carboxyl-terminal domain substrate recognition.
Fisher et al., New York City, United States. In Mol Cell Biol, 2012
a Cdk9 carboxyl-terminal extension, distinct from the catalytic domain, mediates binding to both Pcm1 and the Pol II carboxyl-terminal domain
Phosphorylation by cyclin-dependent kinase-9 controls ubiquitin-conjugating enzyme-2A function.
Johnsen et al., Göttingen, Germany. In Cell Cycle, 2012
CDK9 phosphorylates UBE2A and regulates UBE2A-mediated monoubiquitination of both H2B and PCNA.
TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial.
Leifke et al., Ann Arbor, United States. In Lancet, 2012
We aimed to assess whether selective pharmacological activation of this receptor by TAK-875 in patients with type 2 diabetes mellitus improved glycaemic control without hypoglycaemia risk.
Cyclin-dependent kinase 7/9 inhibitor SNS-032 abrogates FIP1-like-1 platelet-derived growth factor receptor α and bcr-abl oncogene addiction in malignant hematologic cells.
Pan et al., Guangzhou, China. In Clin Cancer Res, 2012
Data show that the cyclin-dependent kinase 7/9 inhibitor (CDK7/9 inhibitor) potently inhibits FIP1L1-PDGFRalpha-positive Bcr-Abl-positive chronic myeloid leukemia (CML) cells.
Flavopiridol induces phosphorylation of AKT in a human glioblastoma cell line, in contrast to siRNA-mediated silencing of Cdk9: Implications for drug design and development.
Giordano et al., Philadelphia, United States. In Cell Cycle, 2012
siRNA-mediated inhibition of Cdk9 caused a shift from G 0/G 1 to G 2/M phase in human PC3 prostate cancer cell line.
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