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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, HAD
Papers using TAK antibodies
Identification of the vesicular nucleotide transporter (VNUT) in taste cells.
Supplier
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
Supplier
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
Systematic Determination of Human Cyclin Dependent Kinase (CDK)-9 Interactome Identifies Novel Functions in RNA Splicing Mediated by the DDX5/17 RNA Helicases.
New
Brasier et al., United States. In Mol Cell Proteomics, 24 Aug 2015
Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of transcriptional elongation activating resting RNA polymerase engaged with of innate immune response (IIR) genes.
MicroRNA34a enhances HIV-1 replication by targeting PNUTS/PPP1R10 which negatively regulates HIV-1 transcriptional complex formation.
New
Banerjea et al., New Delhi, India. In Biochem J, 17 Aug 2015
We report for the first time that PNUTS negatively regulates HIV-1 transcription by inhibiting the assembly of core components of P-TEFb i.e.
[New therapies in metastatic castration resistant prostate cancer].
Review
New
Massard et al., Villejuif, France. In Bull Cancer, 30 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.
Review
New
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.
Reactivation of latent HIV-1 provirus via targeting protein phosphatase-1.
New
Nekhai et al., Washington, D.C., United States. In Retrovirology, Dec 2014
Transcriptional activation, which is prerequisite for reactivation and the eradication of latent proviruses, is impaired in latently infected T cells due to the lack of host transcription factors, primarily NF-κB and P-TEFb (CDK9/cyclin T1).
Signaling mechanisms regulating fibroblast activation, phenoconversion and fibrosis in the heart.
Review
New
Pasumarthi et al., In Indian J Biochem Biophys, Dec 2014
Pathways, including FAK/TAK/JNK and PI3K/Akt/rac have also been implicated in activating phenoconversion of fibroblasts.
Combined transcriptome studies identify AFF3 as a mediator of the oncogenic effects of β-catenin in adrenocortical carcinoma.
New
Ragazzon et al., Paris, France. In Oncogenesis, Dec 2014
AFF3 overexpression in adrenocortical cells interferes with the organization and/or biogenesis of these nuclear speckles and alters the distribution of CDK9 and cyclin T1 such that they accumulate at the sites of AFF3/speckles.
Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.
New
Hussey et al., San Antonio, United States. In Plos One, Dec 2014
For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo.
High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875.
New
Impact
Okada et al., San Diego, United States. In Nature, Oct 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.
Recent advances in Takayasu arteritis.
Review
New
Mimori et al., Kyoto, Japan. In Int J Rheum Dis, Mar 2014
Takayasu arteritis (TAK) is a relatively rare systemic vasculitis mainly affecting the aorta and its large branches.
Changing paradigms in management of metastatic Castration Resistant Prostate Cancer (mCRPC).
Review
Tan et al., Jacksonville, United States. In Bmc Urol, 2013
There are also ongoing phase III trials for Orteronel (TAK- 700), ARN- 509 and Galeterone (TOK-001), which targets androgen signaling.
HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia.
Impact
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.
Impact
GeneRIF
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.
GeneRIF
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.
GeneRIF
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.
Impact
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.
GeneRIF
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.
GeneRIF
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.
RNAP II CTD phosphorylated on threonine-4 is required for histone mRNA 3' end processing.
Impact
Manley et al., New York City, United States. In Science, 2011
Like Ser(2), Thr(4) phosphorylation requires the CTD kinase CDK9 and is evolutionarily conserved from yeast to human.
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