Cdk9

Summary

Gene Symbol: Cdk9
Description: cyclin-dependent kinase 9 (CDC2-related kinase)
Alias: PITALRE, cyclin-dependent kinase 9, cell division protein kinase 9
Species: mouse
Products:     Cdk9

Top Publications

  1. MacLachlan T, Sang N, De Luca A, Puri P, Levrero M, Giordano A. Binding of CDK9 to TRAF2. J Cell Biochem. 1998;71:467-78 pubmed
    b>CDK9 has been recently shown to have increased kinase activity in differentiated cells in culture and a differentiated tissue-specific expression in the developing mouse...
  2. Meier N, Krpic S, Rodriguez P, Strouboulis J, Monti M, Krijgsveld J, et al. Novel binding partners of Ldb1 are required for haematopoietic development. Development. 2006;133:4913-23 pubmed
    ..cells, in particular the repressor protein Eto-2 (and its family member Mtgr1), the cyclin-dependent kinase Cdk9, and the bridging factor Lmo4...
  3. Napolitano G, Licciardo P, Carbone R, Majello B, Lania L. CDK9 has the intrinsic property to shuttle between nucleus and cytoplasm, and enhanced expression of cyclin T1 promotes its nuclear localization. J Cell Physiol. 2002;192:209-15 pubmed
    b>CDK9 in association with cyclin T constitutes the P-TEFb complex that stimulates transcription elongation of RNAPII transcripts by phosphorylation of the CTD of RNAPII...
  4. Elagib K, Mihaylov I, Delehanty L, Bullock G, Ouma K, Caronia J, et al. Cross-talk of GATA-1 and P-TEFb in megakaryocyte differentiation. Blood. 2008;112:4884-94 pubmed publisher
    ..transcriptional elongation factor P-TEFb, a complex containing cyclin T1 and the cyclin-dependent kinase 9 (Cdk9)...
  5. Yang Z, He N, Zhou Q. Brd4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression and cell cycle progression. Mol Cell Biol. 2008;28:967-76 pubmed
    ..It also functions as an associated factor and positive regulator of P-TEFb, a Cdk9-cyclin T1 heterodimer that stimulates transcriptional elongation by phosphorylating RNA polymerase II...
  6. Song S, Kim A, Ragoczy T, Bender M, Groudine M, Dean A. Multiple functions of Ldb1 required for beta-globin activation during erythroid differentiation. Blood. 2010;116:2356-64 pubmed publisher
    ..Ldb1 contributes these critical functions at both embryonic and adult stages of globin gene expression. These results implicate Ldb1 as a factor that facilitates nuclear relocation for transcription activation. ..
  7. Huang C, Lujambio A, Zuber J, Tschaharganeh D, Doran M, Evans M, et al. CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma. Genes Dev. 2014;28:1800-14 pubmed publisher
    ..toward known drug targets in a genetically defined Myc-driven HCC model, we identified cyclin-dependent kinase 9 (Cdk9) as required for disease maintenance...
  8. Sano M, Wang S, Shirai M, Scaglia F, Xie M, Sakai S, et al. Activation of cardiac Cdk9 represses PGC-1 and confers a predisposition to heart failure. EMBO J. 2004;23:3559-69 pubmed
    ..Previously, we showed that hypertrophy is accompanied by activation of cyclin T/Cdk9, which phosphorylates the C-terminal domain of the large subunit of RNA polymerase II, stimulating transcription ..
  9. Padmanabhan K, Robles M, Westerling T, Weitz C. Feedback regulation of transcriptional termination by the mammalian circadian clock PERIOD complex. Science. 2012;337:599-602 pubmed publisher
    ..Circadian clock negative feedback thus includes direct control of transcriptional termination. ..

More Information

Publications44

  1. Dai Q, Lei T, Zhao C, Zhong J, Tang Y, Chen B, et al. Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells. J Biol Chem. 2012;287:25344-52 pubmed publisher
    ..Surprisingly, cyclin K did not interact with CDK9 protein in cells as thought previously...
  2. Devaiah B, Lewis B, Cherman N, Hewitt M, Albrecht B, Robey P, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012;109:6927-32 pubmed publisher
    ..Phosphorylation of the CTD Ser2 is inhibited in vivo by a BRD4 inhibitor that blocks its binding to chromatin. Our finding that BRD4 is an RNA polymerase II CTD Ser2 kinase implicates it as a regulator of eukaryotic transcription. ..
  3. Oqani R, Kim H, Diao Y, Park C, Jin D. The CDK9/cyclin T1 subunits of P-TEFb in mouse oocytes and preimplantation embryos: a possible role in embryonic genome activation. BMC Dev Biol. 2011;11:33 pubmed publisher
    ..Here, we show that the CDK9 and cyclin T1 subunits of P-TEFb are present in mouse oocytes and preimplantation embryos...
  4. Lin S, Coutinho Mansfield G, Wang D, Pandit S, Fu X. The splicing factor SC35 has an active role in transcriptional elongation. Nat Struct Mol Biol. 2008;15:819-26 pubmed publisher
    ..the gene body and attenuated elongation, which are correlated with defective P-TEFb (a complex composed of CycT1-CDK9) recruitment and dramatically reduced CTD Ser2 phosphorylation...
  5. Giacinti C, Musaro A, De Falco G, Jourdan I, Molinaro M, Bagella L, et al. Cdk9-55: a new player in muscle regeneration. J Cell Physiol. 2008;216:576-82 pubmed publisher
    ..We have previously reported that cdk9 is required for myogenesis in vitro by activating MyoD-dependent transcription...
  6. Bagella L, Stiegler P, De Luca A, Siracusa L, Giordano A. Genomic organization, promoter analysis, and chromosomal mapping of the mouse gene encoding Cdk9. J Cell Biochem. 2000;78:170-8 pubmed
    Cdk9, previously known as PITALRE, belongs to the Cdc2 family of protein kinases. We report the isolation and characterization of the complete gene coding for the murine Cdk9 protein...
  7. Giacinti C, Bagella L, Puri P, Giordano A, Simone C. MyoD recruits the cdk9/cyclin T2 complex on myogenic-genes regulatory regions. J Cell Physiol. 2006;206:807-13 pubmed
    ..We show that MyoD recruits cdk9/cyclin T2, together with the histone acetyltransferases p300 and PCAF, and the chromatin remodeling complex SWI/SNF,..
  8. Espinoza Derout J, Wagner M, Shahmiri K, Mascareno E, Chaqour B, Siddiqui M. Pivotal role of cardiac lineage protein-1 (CLP-1) in transcriptional elongation factor P-TEFb complex formation in cardiac hypertrophy. Cardiovasc Res. 2007;75:129-38 pubmed
    ..We performed immunoblot and immunofluorescence analysis of CLP-1 and the P-TEFb components cdk9 and cyclin T in fetal mouse heart and 2 day post-natal mouse cardiomyocytes to determine if they are co-localized...
  9. He N, Pezda A, Zhou Q. Modulation of a P-TEFb functional equilibrium for the global control of cell growth and differentiation. Mol Cell Biol. 2006;26:7068-76 pubmed
    ..Concurrently, the P-TEFb equilibrium was shifted overwhelmingly toward the 7SK snRNP side. Together, these data link the P-TEFb equilibrium to the intracellular transcriptional demand and proliferative/differentiated states of cells. ..
  10. Proserpio V, Fittipaldi R, Ryall J, Sartorelli V, Caretti G. The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the myostatin and c-Met genes and regulates skeletal muscle atrophy. Genes Dev. 2013;27:1299-312 pubmed publisher
  11. Iankova I, Petersen R, Annicotte J, Chavey C, Hansen J, Kratchmarova I, et al. Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis. Mol Endocrinol. 2006;20:1494-505 pubmed
    ..The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K)...
  12. Bottardi S, Mavoungou L, Bourgoin V, Mashtalir N, Affar E, Milot E. Direct protein interactions are responsible for Ikaros-GATA and Ikaros-Cdk9 cooperativeness in hematopoietic cells. Mol Cell Biol. 2013;33:3064-76 pubmed publisher
    ..Here, we established that the Ik interactions with GATA transcription factors and cyclin-dependent kinase 9 (Cdk9), a component of the positive transcription elongation factor b (P-TEFb), are required for transcriptional ..
  13. Kaichi S, Takaya T, Morimoto T, Sunagawa Y, Kawamura T, Ono K, et al. Cyclin-dependent kinase 9 forms a complex with GATA4 and is involved in the differentiation of mouse ES cells into cardiomyocytes. J Cell Physiol. 2011;226:248-54 pubmed publisher
    ..Recently, we demonstrated that cyclin-dependent kinase 9 (Cdk9), a core component of positive elongation factor-b, is a novel GATA4-binding partner...
  14. Kohoutek J, Li Q, Blazek D, Luo Z, Jiang H, Peterlin B. Cyclin T2 is essential for mouse embryogenesis. Mol Cell Biol. 2009;29:3280-5 pubmed publisher
    ..In mammals, it contains predominantly the C-type cyclin cyclin T1 (CycT1) or CycT2 and cyclin-dependent kinase 9 (Cdk9)...
  15. Alarcon C, Zaromytidou A, Xi Q, Gao S, Yu J, Fujisawa S, et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell. 2009;139:757-69 pubmed publisher
    ..Smads form transcriptional complexes, they are phosphorylated at an interdomain linker region by CDK8 and CDK9, which are components of transcriptional mediator and elongation complexes...
  16. Oven I, Brdicková N, Kohoutek J, Vaupotic T, Narat M, Peterlin B. AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells. Mol Cell Biol. 2007;27:8815-23 pubmed
    ..Our findings reveal critical steps by which AIRE regulates the transcription of genes that control central tolerance in the thymus. ..
  17. Biswas D, Milne T, Basrur V, Kim J, Elenitoba Johnson K, Allis C, et al. Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes. Proc Natl Acad Sci U S A. 2011;108:15751-6 pubmed publisher
    ..Thus, our study provides direct mechanistic insight into the role of fusion partners in MLL fusion-mediated leukemogenesis. ..
  18. Gaucher J, Boussouar F, Montellier E, Curtet S, Buchou T, Bertrand S, et al. Bromodomain-dependent stage-specific male genome programming by Brdt. EMBO J. 2012;31:3809-20 pubmed publisher
  19. Salem T, Gomard T, Court F, Moquet Torcy G, Brockly F, Forné T, et al. Chromatin loop organization of the junb locus in mouse dendritic cells. Nucleic Acids Res. 2013;41:8908-25 pubmed publisher
    ..Thus, our work unveils a novel topological framework underlying fast junb transcriptional response in DCs. Moreover, it also points to a novel layer of complexity in the modes of action of NF-?B. ..
  20. Ji X, Zhou Y, Pandit S, Huang J, Li H, Lin C, et al. SR proteins collaborate with 7SK and promoter-associated nascent RNA to release paused polymerase. Cell. 2013;153:855-68 pubmed publisher
    ..These findings reveal an unanticipated SR protein function, a role for promoter-proximal nascent RNA in gene activation, and an analogous mechanism to HIV Tat/TAR for activating cellular genes. ..
  21. Bezstarosti K, Ghamari A, Grosveld F, Demmers J. Differential proteomics based on 18O labeling to determine the cyclin dependent kinase 9 interactome. J Proteome Res. 2010;9:4464-75 pubmed publisher
    ..between bona fide interaction partners of the low-level expressing cell cycle regulator cyclin-dependent kinase 9 (Cdk9) and nonspecifically binding or background proteins...
  22. Pirngruber J, Shchebet A, Schreiber L, Shema E, Minsky N, Chapman R, et al. CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing. EMBO Rep. 2009;10:894-900 pubmed publisher
    ..Cyclin-dependent kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional regulatory proteins, including the RNA polymerase II ..
  23. Takaya T, Ono K, Kawamura T, Takanabe R, Kaichi S, Morimoto T, et al. MicroRNA-1 and MicroRNA-133 in spontaneous myocardial differentiation of mouse embryonic stem cells. Circ J. 2009;73:1492-7 pubmed
    ..assays revealed that miR-1 recognizes and targets the 3' untranslated region of cyclin-dependent kinase-9 (Cdk9) in ES cells...
  24. Bottardi S, Zmiri F, Bourgoin V, Ross J, Mavoungou L, Milot E. Ikaros interacts with P-TEFb and cooperates with GATA-1 to enhance transcription elongation. Nucleic Acids Res. 2011;39:3505-19 pubmed publisher
    ..In agreement with the latter, we show that Ikaros interacts with Cyclin-dependent kinase 9 (Cdk9), which contributes to efficient transcription elongation by phosphorylating the C-terminal domain of the large ..
  25. Sunagawa Y, Morimoto T, Takaya T, Kaichi S, Wada H, Kawamura T, et al. Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes. J Biol Chem. 2010;285:9556-68 pubmed publisher
    ..By tandem affinity purification and mass spectrometric analyses, we identified cyclin-dependent kinase-9 (Cdk9) as a novel GATA4-binding partner. Cdk9 also formed a complex with p300 as well as GATA4 and cyclin T1...
  26. Barrôco R, De Veylder L, Magyar Z, Engler G, Inze D, Mironov V. Novel complexes of cyclin-dependent kinases and a cyclin-like protein from Arabidopsis thaliana with a function unrelated to cell division. Cell Mol Life Sci. 2003;60:401-12 pubmed
    ..These CDKs share a PITAIRE signature in the cyclin-binding domain and the structural characteristics of mammalian CDK9. Yeast two-hybrid screens and immunoprecipitation assays identified CDKC-interacting proteins with homology to the ..
  27. Galatioto J, Mascareno E, Siddiqui M. CLP-1 associates with MyoD and HDAC to restore skeletal muscle cell regeneration. J Cell Sci. 2010;123:3789-95 pubmed publisher
    ..These findings suggest a novel transcriptional paradigm whereby CLP-1, in conjunction with MyoD and HDAC, acts to inhibit growth-related gene expression, a requirement for myoblasts to exit the cell cycle and transit to myotubes. ..
  28. Okamura D, Maeda I, Taniguchi H, Tokitake Y, Ikeda M, Ozato K, et al. Cell cycle gene-specific control of transcription has a critical role in proliferation of primordial germ cells. Genes Dev. 2012;26:2477-82 pubmed publisher
    ..These results indicate that CDKI gene-specific control of transcription by 7SK snRNP plays a pivotal role in the maintenance of PGC proliferation. ..
  29. Bagella L, MacLachlan T, Buono R, Pisano M, Giordano A, De Luca A. Cloning of murine CDK9/PITALRE and its tissue-specific expression in development. J Cell Physiol. 1998;177:206-13 pubmed
    ..We previously cloned a cdc2-related kinase, cdk9/PITALRE, that is able to phosphorylate the retinoblastoma protein in vitro...
  30. Zhan Y, Han Y, Sun H, Liang T, Zhang C, Song J, et al. Down-regulating cyclin-dependent kinase 9 of alloreactive CD4+ T cells prolongs allograft survival. Oncotarget. 2016;7:24983-94 pubmed publisher
    b>CDK9 (Cyclin-dependent kinase 9)/Cyclin T1/RNA polymerase II pathway has been demonstrated to promote the development of several inflammatory diseases, such as arthritis or atherosclerosis, however, its roles in allotransplantation ..
  31. Rahl P, Lin C, Seila A, Flynn R, McCuine S, Burge C, et al. c-Myc regulates transcriptional pause release. Cell. 2010;141:432-45 pubmed publisher
    ..We discuss the implications of these results for the role of c-Myc amplification in human cancer. ..
  32. Nojima M, Huang Y, Tyagi M, Kao H, Fujinaga K. The positive transcription elongation factor b is an essential cofactor for the activation of transcription by myocyte enhancer factor 2. J Mol Biol. 2008;382:275-87 pubmed publisher
  33. Di Stefano B, Collombet S, Jakobsen J, Wierer M, Sardina J, Lackner A, et al. C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4. Nat Cell Biol. 2016;18:371-81 pubmed publisher
    ..post-transcriptionally increases the abundance of several hundred proteins, including Lsd1, Hdac1, Brd4, Med1 and Cdk9, components of chromatin-modifying complexes present at super-enhancers...
  34. Oqani R, Lin T, Lee J, Kim S, Sa S, Woo J, et al. Inhibition of P-TEFb disrupts global transcription, oocyte maturation, and embryo development in the mouse. Genesis. 2016;54:470-82 pubmed publisher
    ..In this study, using immunocytochemical analyses, we find that the P-TEFb components, Cyclin T1, CDK9, and its T-loop phosphorylated form, are localized to nuclear speckles, as well as in nucleoli in mouse germinal ..
  35. Simone C, Stiegler P, Bagella L, Pucci B, Bellan C, De Falco G, et al. Activation of MyoD-dependent transcription by cdk9/cyclin T2. Oncogene. 2002;21:4137-48 pubmed
    ..Unlike the other cdks, cdk9 is not serum- or cell cycle-regulated and is instead involved in the regulation of transcriptional elongation by ..