ライフサイエンスコーパス: CDK9

1 ith NF-kappaB and cyclin-dependent kinase 9 (CDK9).

2 ific inhibitor of cyclin-dependent kinase 9 (Cdk9).

3 ain 4 (Brd4), and cyclin-dependent kinase 9 (CDK9).

4 ol processes such as transcription (Cdk7 and Cdk9).

5 cyclin T1 and the cyclin-dependent kinase 9 (Cdk9).

6 pproximately 100 members for CDK1, CDK7, and CDK9.

7 revealed that FIT-039 specifically inhibited CDK9.

8 targets of Cavity 1 and Cavity 2 regions on CDK9.

9 d by IRF3-dependent recruitment of activated CDK9.

10 Ser-81 and activated by the transcriptional CDK9.

11 tase M1A in normally growing cells activates CDK9.

12 tor b (P-TEFb), the complex of cyclin T1 and CDK9.

13 cs6 stimulates subsequent phosphorylation by Cdk9.

14 by and is phosphorylated by Cdk7 but not by Cdk9.

15 inhibitory activity against Cdk2, Cdk7, and Cdk9.

16 benzimidazole (DRB), a specific inhibitor of cdk9.

17 mammalian cdc2-related kinase, CRK7, than to CDK9.

18 s of CRK7 that make the latter distinct from CDK9.

19 in-dependent kinases (CDKs): CDK7, CDK8, and CDK9.

20 as a regulatory subunit for the activity of Cdk9.

21 plexes, Hexim1 cross-links and thus contacts Cdk9.

22 l lines by blocking the activity of CDK2 and CDK9.

23 in-dependent kinases (CDK)1, CDK2, CDK5, and CDK9.

24 12 but was still 10-fold more potent towards Cdk9.

25 olymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthes

26 g the activity of cyclin-dependent kinase 9 (CDK9), a protein required for recovery from replication

27 ruitment coincided with increased binding of Cdk9, a component of P-TEFb and RNA polymerase II to the

28 oteomic studies demonstrated that RBPJ binds CDK9, a component of positive transcription elongation f

29 in part via blocking the phosphorylation of CDK9, a p-TEFb complex member that serves as a cofactor

30 omplex containing cyclin dependent kinase-9 (CDK9; a kinase necessary for triggering transcriptional

31 n, but the precise mechanisms and targets of Cdk9 action remain largely unknown.

32 Fb), which is composed of CycT1 or CycT2 and CDK9, activates eukaryotic transcription elongation.

33 esults from the relative malleability of the CDK9 active site rather than from the formation of speci

34 CDK9 activity and recognition of regulatory proteins are

35 c targets in NB and that abrogating CDK2 and CDK9 activity by small molecules like dinaciclib is a pr

36 CDK9 activity decreases the pause duration but also incr

37 Our data demonstrate a pivotal role of Cdk9 activity for coupling of RNAPII transcription with

38 The requirement of CDK9 activity for ISG expression was shown by siRNA-medi

39 Inhibiting CDK9 activity in peripheral blood mononuclear cells resu

40 CDK9 activity is also associated with long-range chromat

41 CDK9 activity may be a target for immunomodulation in RS

42 ic inhibition both confirmed contribution of Cdk9 activity to megakaryocytic differentiation.

43 ophy that is accompanied with an increase in cdk9 activity via an increase in serine 2 phosphorylatio

44 cture of 7SK, a noncoding RNA that regulates Cdk9 activity.

45 Moreover, wild-type, but not acetylated CDK9, alleviates the replication stress response impairm

46 s, and common core structures used to target CDK9, along with their selectivity profile and efficacy

47 t.P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also kno

48 ation of Hexim1 and 7SK snRNA from cyclin T1/CDK9 and activates the transcriptional activity of P-TEF

49 ls, an active form composed of cyclin T1 and CDK9 and an inactive form, in which cyclin T1/CDK9 is se

50 ion was shown by siRNA-mediated silencing of CDK9 and by a selective CDK9 inhibitor in A549 cells.

51 dings reveal a mechanism involving PP1alpha, CDK9 and CDK1 that is used by AR to initiate and sustain

52 By inhibiting CDK7, CDK9 and CDK12, these inhibitors transiently reduce RNA

53 X-ray crystal structures of 12u bound to CDK9 and CDK2 provide insights into the binding modes.

54 An inhibitor of CDK9 and CDK7 CTD kinase activities, TAF7 also binds to

55 Consistent with its action against Cdk9 and Cdk7, SNS-032 inhibited the phosphorylation of

56 following orthology relationships: Bur1 <--> CDK9 and Ctk1 <--> CDK12/13.

57 on elongation factor b (P-TEFb, a complex of CDK9 and cyclin T), we examined whether inhibition of RN

58 n elongation factor b (P-TEFb), a complex of Cdk9 and cyclin T1, promotes release of paused Pol II in

59 In addition, cdk9 and ICP22 appeared to colocalize with RNA Pol II in

60 change, which promotes its interaction with CDK9 and increases BRD4's transcriptional activity.

61 r(4) phosphorylation requires the CTD kinase CDK9 and is evolutionarily conserved from yeast to human

62 indicated that Atf4 directly interacts with CDK9 and its associated protein cyclin T1.

63 ide evidence of a direct interaction between Cdk9 and its inhibitor, Hexim1.

64 The primary function of cdk9 and its partners, the cyclin T variants, is in the

65 inhibition of histone acetyltransferases and CDK9 and less sensitivity to histone deacetylase inhibit

66 H-associated kinase Mcs6 and P-TEFb homologs Cdk9 and Lsk1 of fission yeast, making them sensitive to

67 on levels and depended on the role that both CDK9 and MYC exert in transcription elongation.

68 xpression depend on physical linkage between Cdk9 and Pcm1.

69 ab with a nanomolar potency against CDK2 and CDK9 and potent antiproliferative activities against a p

70 expression by impairing its interaction with CDK9 and suppresses gastric cancer cell proliferation, m

71 ined through the differential recruitment of CDK9 and the control of transcription elongation.

72 posed to interfere with substrate binding to Cdk9 and thereby to inhibit its kinase activity.

73 Cyclin-dependent kinase 9 (CDK9) and CDK12 have each been demonstrated to phosphory

74 EFb), composed of cyclin-dependent kinase 9 (CDK9) and cyclin T, is a global transcription factor for

75 Fb), comprised of cyclin-dependent kinase 9 (CDK9) and cyclins T1 (CycT1) or T2 (CycT2), activates eu

76 taining HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1).

77 We report that three CTD kinases, CDK7, CDK9, and BRD4, engage in cross-talk, modulating their s

78 DKC2 combines the functions of both CRK7 and CDK9, and could also couple splicing with transcription.

79 AR in complex with HIV-1 Tat and human AFF4, CDK9, and CycT1.

80 PPM1A and Cdk9 appear to associate in vivo as the proteins could b

81 The Pol II elongation factors Elongin-A and Cdk9 are essential for optimal Ubx and Abd-B expression.

82 form where the core components cyclin T1 and CDK9 are incorporated in the 7SK small nuclear ribonucle

83 Consistently, phospho-GRIP1 and CDK9 are not detected at GR transrepression sites near p

84 together, this study suggests that CDK2 and CDK9 are potential therapeutic targets in NB and that ab

85 evels of Cyclin T1 and T-loop-phosphorylated CDK9 are very low but increase significantly upon cellul

86 in T1 (CycT1) and cyclin-dependent kinase 9 (CDK9), are required for LTR-directed HIV-1 transcription

87 ated in NUT midline carcinoma and identified CDK9 as a potential kinase mediating BRD4 hyperphosphory

88 el, we identified cyclin-dependent kinase 9 (Cdk9) as required for disease maintenance.

89 CDK9, as part of P-TEFb and the super elongation complex

90 lar Cell, Jeronimo et al. identify BCDIN3, a Cdk9-associated protein, as the enzyme that forms the di

91 sphorylation mediates RelA acetylation, Brd4/CDK9 association, and activation of downstream inflammat

92 BRD4 phosphorylates PTEFb/CDK9 at either Thr-29 or Thr-186, depending on its relat

93 SIRT2 interacts with and deacetylates CDK9 at lysine 48 in response to replication stress in a

94 does so by promoting the phosphorylation of CDK9 at the T-loop, liberating P-TEFb from the inactive

95 required for recruitment and maintenance of cdk9 at the viral transcriptosomes.

96 Brd4 induces phosphorylation of CDK9 at threonine 29 (T29) in the HIV transcription init

97 nd also the recruitment of the Pol II kinase CDK9, at the DioI promoter.

98 BRD4 is required for stable CDK9 binding, phospho-Ser 2 RNA Pol II formation, and hi

99 Selective inhibition of Mcs6 or Cdk9 blocks cell division, alters RNA polymerase (Pol) I

100 d 2 novel cellular partners of Vif, Brd4 and Cdk9, both of which are known to regulate cell-cycle pro

101 T1A change abolished CTD phosphorylation by Cdk9 but did not affect CTD binding to the capping enzym

102 ICP22 binds the cyclin-dependent kinase 9 (cdk9) but not cdk7, and this complex in conjunction with

103 l inhibits Cdk9, we found that inhibition of Cdk9 by DRB or by siRNA could recapitulate the flavopiri

104 We confirmed the interaction of Vif and Cdk9 by immunoprecipitation and Western blot, and showed

105 vated fraction of cyclin-dependent kinase 9 (CDK9) by promoting its association with bromodomain 4 (B

106 ve transcription elongation factor-b) (CycT1:CDK9) C-terminal domain (CTD) kinase to the HIV-1 promot

107 Here we show that a Cdk9 carboxyl-terminal extension, distinct from the cata

108 tivation segment that controls access to the Cdk9 catalytic cleft.

109 Knockdown of Cdk9 caused a strong reduction of the levels of RNAPII-t

110 HNRNPL interactions with P-TEFb components (CDK9, CCNT2, HEXIM1, and the small 7SK RNA).

111 CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6.

112 x (SEC), is by far the best characterized of CDK9, CDK12, and CDK13.

113 ich is critical for its inhibitory effect on CDK9, changed HEXIM1 into an activator.

114 utants indicates that binding of Brd4 to the cdk9 complex is not required but that efficient binding

115 Therefore, fission yeast Cdk9 comprises a catalytic domain sufficient for primed

116 tive abundance, which represses or activates CDK9 CTD kinase activity, respectively.

117 P-TEFb comprises the Cdk9 cyclin-dependent kinase and a cyclin T.

118 n, which recruits cyclin-dependent kinase 9 (CDK9)/cyclin T1 and other host transcriptional coactivat

119 signal-induced, reversible release of active Cdk9-cyclin T modules from large, inactive 7SK small nuc

120 transcriptional elongation factor P-TEFb, a CDK9-cyclin T1 heterodimer that is part of the super elo

121 d factor and positive regulator of P-TEFb, a Cdk9-cyclin T1 heterodimer that stimulates transcription

122 transcription elongation factor b (P-TEFb) (CDK9/cyclin T (CycT)) promotes mRNA transcriptional elon

123 dine-5-carbonitrile series that bind to both CDK9/cyclin T and CDK2/cyclin A.

124 A, we conclude that selective inhibition of CDK9/cyclin T by members of the 4-(thiazol-5-yl)-2-(phen

125 Additionally, cdk9/cyclin T in the presence of Tat is able to phosphor

126 he basis of 11 cocrystal structures bound to CDK9/cyclin T or CDK2/cyclin A, we conclude that selecti

127 P-TEFb (CDK9/cyclin T) plays a central role in androgen receptor

128 during autophagy, inhibition or knockdown of Cdk9/cyclin T1 transcriptionally downregulated SQSTM1/p6

129 CDK9/cyclin T1, a key enzyme in HIV-1 transcription, is

130 elators inhibited the activities of CDK2 and CDK9/cyclin T1, suggesting that inhibition of CDK9 may c

131 omplex may have a role similar to the animal CDK9-CycT complex of the positive transcription elongati

132 d in an open conformation similar to that of Cdk9/CycT but different from those of cell cycle kinases

133 binant Cdk7-CycH-Mat1 as well as recombinant Cdk9-CycT1 phosphorylated CTD Ser7 and Ser5 residues in

134 in, we have determined the structures of the CDK9/CycT1 and free cyclin T2.

135 There are distinct differences between CDK9/CycT1 and the cell cycle CDK CDK2/CycA manifested b

136 red compounds were evaluated in an enzymatic CDK9/CycT1 assay.

137 We show that CDK9/CycT1 autophosphorylates on Thr186 in the activatio

138 nificant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be

139 op novel and selective phosphorus containing CDK9/CycT1 inhibitors.

140 The CDK9/CycT1 interface is relatively sparse but retains so

141 ighly specific, ATP-competitive inhibitor of CDK9/CycT1 with antiviral activity.

142 A kinase-inactive cdk9 (D167N) expressed during the infection also localiz

143 Finally, inhibition of CDK1 and CDK9 decreased AR Ser-81 phosphorylation, chromatin bind

144 ased PD activity with inhibition of Cdk7 and Cdk9, decreases in Mcl-1 and XIAP expression level, and

145 ate genes is, at least in part, regulated by CDK9 dependent co- and/or post-transcriptional events in

146 hese Nup98-dependent virus-induced genes are Cdk9-dependent and translation-independent suggesting th

147 diated changes in pTEFb activity may trigger Cdk9-dependent Smad3 signaling that can modulate collage

148 CDK9 dephosphorylation mobilizes P-TEFb from an inhibito

149 o enhancers, allowing the recruitment of the CDK9 elongating kinase.

150 protein SKIP/SNW1 associates with the P-TEFb/CDK9 elongation factor and coactivates inducible genes,

151 ockdown and CRISPR/cas9-mediated knockout of CDK9 enhances inflammation resolution by reducing neutro

152 by RNAi, flavopiridol, or dominant negative CDK9 expression correlates with loss of phosphorylation

153 inase activity of cyclin-dependent kinase 9 (CDK9) for the phosphorylation of DRB sensitivity-inducin

154 Cdk9 has been characterized as the catalytic subunit of

155 Recently CDK9 has emerged as a druggable target for the developme

156 eads to inhibition of the kinase activity of Cdk9 has remained elusive, however.

157 which is recruited into GC-induced GR:GRIP1:CDK9 hetero-complexes, producing distinct GRE-specific G

158 cription from latently infected cells, via a CDK9/HMBA inducible protein-1 dependent process.

159 ssion of Cyclin T1, or its catalytic partner Cdk9, impaired development of Th1 cells and protective s

160 ent to the chromatin of the P-TEFb component CDK9 in a BRD2-4-dependent manner.

161 regulated by ICP22 and that one function of cdk9 in HSV-1-infected cells may be to bring ICP22 into

162 of experiments designed to probe the role of cdk9 in infected cells.

163 demonstrate the requirement for Mediator and CDK9 in YAP-driven phenotypes of overgrowth and tumorige

164 n of HSF1, PKAcalpha, or the pTEFb component CDK9, indicating a key role for the HSF1-PKA cascade in

165 se results show that transient inhibition of CDK9 induces apoptosis in leukocyte subsets and modulate

166 II clinical trials, binds to the ATP site of CDK9 inducing unanticipated structural changes that bury

167 small interfering RNAs (siRNAs) specific for Cdk9 inhibit the Vif-mediated G- to-S transition.

168 Our results establish CDK9 inhibition as a therapeutic strategy for MYC-overex

169 ripts and that this transition is blocked by CDK9 inhibition in both A549 and primary human small air

170 Pharmacological or shRNA-mediated CDK9 inhibition led to robust anti-tumor effects that co

171 The effects of CDK9 inhibition on RNA levels and protein expression, ap

172 mice with megakaryocytic GATA-1 deficiency, Cdk9 inhibition produced a fulminant but reversible mega

173 CDK9 inhibition selectively targets survival proteins an

174 n (IFN-beta) expression is not influenced by CDK9 inhibition.

175 llapse of global elongation that phenocopies CDK9 inhibition.

176 ongly upregulated by treating cells with the CDK9 inhibitor flavopiridol.

177 ediated silencing of CDK9 and by a selective CDK9 inhibitor in A549 cells.

178 We find that flavopiridol, a CDK9 inhibitor that blocks transcription elongation, inh

179 ment of GATA-1 and dissociation of HEXIM1, a Cdk9 inhibitor.

180 we focused on the cyclin-dependent kinase 9 (CDK9) inhibitor, FIT-039, which suppressed replication o

181 Infection in the presence of the cdk9 inhibitors Flavopiridol and DRB (5,6-dichloro-1-bet

182 ied anthracyclines including doxorubicin and CDK9 inhibitors including dinaciclib that synergized wit

183 trategy as cyclin-dependent kinases CDK2 and CDK9 inhibitors, which play critical roles in the cell c

184 gen type II and treated orally with specific CDK9 inhibitors.

185 with regard to the development of selective CDK9 inhibitors.

186 in disease severity following treatment with CDK9 inhibitors.

187 eriolins correlates best with their CDK2 and CDK9 inhibitory activity.

188 Our data show that CDK9 is a possible target for controlling resolution of

189 iptional paused genes mediated by the kinase Cdk9 is also required for Pvf2 production.

190 pharmacological and genetic approaches, that CDK9 is involved in the resolution of neutrophil-depende

191 ptosomes, indicating that kinase activity of cdk9 is not a requirement for its localization to the si

192 DK9 and an inactive form, in which cyclin T1/CDK9 is sequestered by Hexim1 and 7SK snRNA.

193 Cdk9 is the catalytic subunit of a general RNA polymeras

194 P-TEFb complex, composed of cyclin T and cdk9, is critical for elongation of nascent RNA chains v

195 a cellular kinase composed of Cyclin T1 and CDK9, is essential for processive HIV-1 transcription.

196 Here we review the regulation of CDK9, its cellular functions, and common core structures

197 ) but not cyclin T or K, thereby stimulating CDK9 kinase activity and promoting recovery from replica

198 bsequent events through which Brd4 regulates CDK9 kinase activity and RNAP II-dependent transcription

199 I on the gamma-FBG promoter, indicating that CDK9 kinase activity mediates IL-6-inducible CTD phospho

200 n complex, CTIP2 significantly represses the Cdk9 kinase activity of P-TEFb.

201 transcription initiation complex, inhibiting CDK9 kinase activity.

202 nd Pol II CTD S2A mutations heralds that the Cdk9 kinase has an essential target other than Spt5 and

203 ubunit but makes no stable contacts with the CDK9 kinase subunit.

204 bstrate for threonine phosphorylation by the Cdk9 kinase.

205 hich IE2 gene expression is greatly reduced, cdk9 localization at the transcriptosome is delayed and

206 We found that cdk9 localization to the viral transcriptosomes requires

207 1-beta-D-ribofuranosylbenzimidazole) allowed cdk9 localization to the viral transcriptosomes.

208 Notably, BRD4 loss does not directly affect CDK9 localization.

209 scription such as cyclin-dependent kinase 9 (cdk9), localize at these sites.

210 ion of the various reaction components: GR < Cdk9 < BRD4 </= induced gene < NELF-E.

211 DK9/cyclin T1, suggesting that inhibition of CDK9 may contribute to the inhibition of HIV-1 transcrip

212 e in transcription regulation; specifically, CDK9 mediated transcriptional regulation of short-lived

213 alpha), resulting in P-TEFb mobilization and CDK9-mediated AR S81 phosphorylation.

214 restricts actions of its own coregulator via CDK9-mediated phosphorylation to a subset of anti-inflam

215 ciation with pTEFb causing inhibition of the Cdk9-mediated serine 2 phosphorylation in the carboxyl-t

216 with small interfering RNA (siRNA) targeting cdk9 mRNAs.

217 Exogenous expression of additional cdk9 mutants indicates that binding of Brd4 to the cdk9

218 reported that the serine kinase activity of Cdk9 not only targets RNA polymerase II but also the con

219 Dephosphorylation of CDK9 on Thr(186) by protein phosphatase 1 (PP1) in stres

220 lex of STAT3 with cyclin-dependent kinase 9 (CDK9) on gamma-FBG expression in HepG2 hepatocarcinoma c

221 Targeting CDK9 or c-MYC, an upstream regulator of RBPJ, with small

222 Conversely, inhibition or depletion of Cdk9 or mutation of Xrn2-Thr439 to a nonphosphorylatable

223 Phosphorylation by Cdk9 or phosphomimetic substitution of its target residu

224 ependent growth arrest was rescued by the dn-Cdk9- or Cdk9-specific short hairpin RNA in SaOS2 cells.

225 CDK7, CDK9 (P-TEFb), and CDK13 are also critical for HIV repli

226 y is sufficient-and necessary-to recruit the Cdk9/Pcm1 (mRNA cap methyltransferase) complex.

227 Removal of this segment diminishes Cdk9/Pcm1 chromatin recruitment and Spt5 phosphorylation

228 on similarities with Cdk2 3D structure, the Cdk9 peptide cross-linked by Hexim1 corresponds to the s

229 also find that BRD4 independently regulates CDK9/phospho-Ser 2 CTD RNA Pol II recruitment to the IRF

230 d immunofluorescence analysis confirmed that CDK9, phosphorylated at serine 175, was recruited to RNA

231 Conversely, CDK9 phosphorylates BRD4 enhancing its CTD kinase activi

232 Stable expression of cdNIPP1 increased CDK9 phosphorylation on Thr(186) and the association of

233 of NFkappaB signaling and the regulation of Cdk9 phosphorylation status.

234 We conclude that cdk9 plays a critical role in the optimization of expres

235 CDK9 plays a crucial role in transcription regulation; s

236 ion was mediated by the recruitment of IRF3, CDK9, polymerase II (Pol II), and phospho-Ser(2) carboxy

237 zol moiety and investigated their effects on CDK9 potency and selectivity.

238 On defined peptide substrates in vitro, Cdk9 prefers CTD repeats phosphorylated at Ser7 over unm

239 D), elongation factor Spt5, and the Cdk7 and Cdk9 protein kinases is thought to comprise a transcript

240 down-regulated apoptosis by lowering Bim and Cdk9 proteins in recipient cells.

241 replication stress through deacetylation of CDK9, providing insight into how SIRT2 maintains genome

242 inks MYC and transcriptional control through CDK9, providing potential nodes of fragility for therape

243 We show that both Cdk7 and Cdk9/PTEFb contribute to phosphorylation of Pol II CTD S

244 how that CDKN1C interacts with both CDK7 and CDK9 (putative RNA pol II CTD kinases) and that CDKN1C b

245 inding sites were necessary for HMBA-induced CDK9 recruitment and LTR expression.

246 anscription elongation through cyclin T1 and Cdk9 recruitment and Pol II Ser2 phosphorylation.

247 of RelA recruitment inhibition is a loss of CDK9 recruitment, preventing the stimulation of transcri

248 4 is required for cyclin-dependent kinase 9 (CDK9) recruitment and phospho-Ser 2 carboxy-terminal dom

249 HMBA triggered cyclin-dependent kinase 9 (CDK9) recruitment to the LTR, a key factor in the induct

250 ntiated macrophages, while the expression of CDK9 remained constant.

251 il region of CDK9, unlike the binding of the CDK9-selective inhibitor 5,6-dichlorobenzimidazone-1-bet

252 hibitor design and rationalize the basis for CDK9 selectivity, we have studied the CDK-binding proper

253 e functional role of CDK9 was examined using CDK9 small interfering RNA (siRNA) and CDK inhibitors, w

254 CDK9 specific inhibitors may be a potential alternative

255 growth arrest was rescued by the dn-Cdk9- or Cdk9-specific short hairpin RNA in SaOS2 cells.

256 ings indicate that Ser-81 phosphorylation by CDK9 stabilizes AR chromatin binding for transcription a

257 This shows that CDK9 stimulates release of paused polymerase and activat

258 The RSV-induced binding patterns of the CDK9 substrate, phospho-Ser2 RNA polymerase (Pol) II, fo

259 ry histidine-rich domain that interacts with CDK9 substrates including RNA polymerase II.

260 t of P-TEFb, but also with the T-loop of the Cdk9 subunit.

261 NA is moderately reduced after inhibition of Cdk9, suggesting that defective 3' processing of rRNA ne

262 uranosylbenzimidazole (DRB), an inhibitor of CDK9, suppresses expression of gamma2 late genes with an

263 ependent on phosphorylation of Thr186 in the CDK9 T loop.

264 PPM1A and the related PPM1B greatly reduced Cdk9 T-loop phosphorylation in vivo.

265 epletion of PPM1A resulted in an increase in Cdk9 T-loop phosphorylation.

266 es accessible for further phosphorylation by Cdk9 that drives the transition to transcription elongat

267 ion factor composed of cyclin T1 (CycT1) and Cdk9 that phosphorylates the C-terminal domain of RNA po

268 and inhibition of cyclin-dependent kinase 9 (CDK9), that regulates these elongation factors, blocked

269 rase-II enzyme (RNAPII-Ser2P), together with CDK9, the component of positive transcription elongation

270 age CDK-selective inhibitor, potently blocks CDK9, the transcriptional regulator of MCL-1.

271 ption program than Notch in BTICs by binding CDK9, thereby affecting Pol II-regulated transcript elon

272 PPM1B only efficiently dephosphorylated Cdk9 Thr-186 in vitro when 7SK RNA was depleted from P-T

273 phosphorylation of Thr-186 in the T-loop of Cdk9 to allow substrates to access the catalytic core of

274 y, we demonstrate that Brd4 further recruits CDK9 to phosphorylate C-terminal domain of RNA polymeras

275 merase II by using the catalytic function of CDK9 to phosphorylate various substrates during transcri

276 repsilon is critical for recruiting MSK1 and Cdk9 to the chromatin and subsequently phosphorylating t

277 by facilitating the recruitment of MSK1 and Cdk9 to the cox-2 promoter, thereby promoting RNA polyme

278 and requirements of specific recruitment of cdk9 to the viral transcriptosomes, infection in the pre

279 longation complex (SEC), containing AFF4 and CDK9, to alleviate RNAPII pausing.

280 or absence of the C-terminal tail region of CDK9, unlike the binding of the CDK9-selective inhibitor

281 7 nM and shows over 80-fold selectivity for CDK9 versus CDK2.

282 HEXIM1 inhibits the kinase activity of CDK9 via interactions between 7SK, HEXIM1, and CycT1.

283 nked by a photoreactive amino acid replacing Cdk9 W193, a tryptophan within this activation segment.

284 The functional role of CDK9 was examined using CDK9 small interfering RNA (siRN

285 the RNA processing factors phosphorylated by Cdk9 was the 5'-to-3' "torpedo" exoribonuclease Xrn2, re

286 talytic component of the elongation complex, CDK9, was important for the transcriptional activity of

287 Because flavopiridol inhibits Cdk9, we found that inhibition of Cdk9 by DRB or by siRN

288 sphatases that dephosphorylate the T-loop of Cdk9, we used a Thr-186-phosphospecific antiserum to scr

289 on of cell lines expressing exogenous mutant cdk9 were performed.

290 serine cluster by cyclin-dependent kinase-9 (CDK9), which is recruited into GC-induced GR:GRIP1:CDK9

291 tic activities of cyclin-dependent kinase 9 (CDK9), which serves as a transcriptional coactivator of

292 at an interdomain linker region by CDK8 and CDK9, which are components of transcriptional mediator a

293 ocytic leukemia cells by inhibiting Cdk7 and Cdk9, which control transcription.

294 s appeared to enhance the phosphorylation of CDK9, which correlated with significantly increased HIV-

295 evels of Cyclin T1 and T-loop-phosphorylated CDK9, which increase upon activation.

296 ic and rapid inhibition of the P-TEFb kinase CDK9, which is implicated in polymerase pause release.

297 aining the 5'-cap methyltransferase Pcm1 and Cdk9, which phosphorylates the RNA polymerase II (Pol II

298 orylation on Thr(186) and the association of CDK9 with 7SK RNA.

299 Future efforts to cotarget PI3K and Cdk9 with drugs such as PIK-75 in AML are warranted.

300 f the most selective compounds, 12u inhibits CDK9 with IC(50) = 7 nM and shows over 80-fold selectivi

301 tin immunoprecipitation studies showing that CDK9 with phosphorylated T29 is associated with the HIV