ライフサイエンスコーパス: CDK9

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

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

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

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

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

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

7 12 but was still 10-fold more potent towards Cdk9.

8 revealed that FIT-039 specifically inhibited CDK9.

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

10 d by IRF3-dependent recruitment of activated CDK9.

11 Ser-81 and activated by the transcriptional CDK9.

12 tase M1A in normally growing cells activates CDK9.

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

14 cs6 stimulates subsequent phosphorylation by Cdk9.

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

16 inhibitory activity against Cdk2, Cdk7, and Cdk9.

17 olymerase II preinitiation complex, MED1 and CDK9.

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

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

20 vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neu

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

22 CDK9 - a component of the transcription elongation compl

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

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

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

26 from chromatin, unexpectedly, independent of CDK9, a presumed NELF kinase.

27 in microglia by disrupting binding of Tat to CDK9, a process key to HIV transcription elongation.

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

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

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

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

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

33 CDK9 activity decreases the pause duration but also incr

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

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

36 Inhibiting CDK9 activity in peripheral blood mononuclear cells resu

37 CDK9 activity is also associated with long-range chromat

38 CDK9 activity may be a target for immunomodulation in RS

39 quired to maintain pausing in the absence of CDK9 activity nor essential for the release of Pol II in

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

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

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

43 Inhibition of CDK9 also suppressed ovarian cancer cell spheroid growth

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

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

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

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

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

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

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

51 YC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuro

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

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

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

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

56 on elongation factor b (P-TEFb), composed of CDK9 and cyclin T, stimulates transcriptional elongation

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

58 ese results suggest that switches comprising Cdk9 and either PP4 or PP1 govern pause release and the

59 It remained unclear whether Cdk9 and H2Bub1 cooperate to regulate the expression of

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 this study was to evaluate the expression of CDK9 and its therapeutic potential in ovarian cancer.

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 nly CDK1, but transcriptional CDKs (CDK7 and CDK9) and cell cycle CDKs (CDK4 and CDK6) as well.

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

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

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

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

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

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

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

85 Our results reveal CDK9 as a novel prognostic biomarker and a promising the

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

87 ut also transcription as well as positioning CDK9 as an RNA processing cofactor.

88 We identify cyclin dependent kinase 9 (CDK9) as a novel binding partner of the mTOR complex sca

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

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

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

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

98 In the nucleus, CDK9 binds to RAPTOR and mLST8, forming CTORC1, to promo

99 In the cytoplasm, CDK9 binds to RICTOR, SIN1, and mLST8, forming CTORC2, a

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

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

102 Cdk7/Kin28, Cdk9/Bur1, and Cdk12/Ctk1 phosphorylate the polymerase a

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

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

105 Inhibition of CDK9 by small interfering RNA or CDK9 inhibitor function

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

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

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

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

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

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

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

113 vates other transcription-associated kinases CDK9, CDK12, and CDK13, invoking a "master regulator" ro

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

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

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

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

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

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

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

121 dence that PTEN interacts with AFF4, RNAPII, CDK9, cyclin T1, XPB and CDK7.

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

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

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

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

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

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

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

129 Cdk9/cyclin T1 (P-TEFb) catalyzes inhibitory phosphoryla

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

131 tro in HIV-1 latency cell lines in a P-TEFb (CDK9/cyclin T1)-dependent manner.

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

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

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

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

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

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

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

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

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

141 n a type I IFN-dependent manner and that the CDK9 deacetylation is essential for STAT1 phosphorylatio

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

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

144 Cdk9-dependence of antisense suppression at specific gen

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 y at these genes was linked to an unexpected CDK9-dependent compensatory feedback loop that elevated

148 to cognate ligands, enabling gene-selective CDK9-dependent pause release.

149 e overlapping but distinct specificities for Cdk9-dependent phosphorylations of Spt5, a factor instru

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

151 CDK9 dephosphorylation mobilizes P-TEFb from an inhibito

152 n-4 in HEK293 cells (i.e. CAVIN1/PTRF, CCT5, CDK9, EIF2S1, EIF4B, MPP7, PARVB, PFKM, and RASIP).

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

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

155 We discovered that CDK9 enhanced MYC protein stability through a previously

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

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

158 CDK9 expression was determined by immunohistochemistry i

159 ED1, and the transcription elongation factor CDK9 for transcription.

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

161 Genetic interactions link Cdk9, H2Bub1 and the histone deacetylase Clr6-CII, while

162 Cdk9 has been characterized as the catalytic subunit of

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

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

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

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

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

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

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

170 IRT2 deacetylates cyclin-dependent kinase 9 (CDK9) in a type I IFN-dependent manner and that the CDK9

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

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

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

174 histone deacetylase Clr6-CII, while combined Cdk9 inhibition and H2Bub1 loss impair Clr6-CII recruitm

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

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

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

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

179 Here, we show that Cdk9 inhibition or H2Bub1 loss induces intragenic antise

180 CDK9 inhibition selectively targets survival proteins an

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

182 llapse of global elongation that phenocopies CDK9 inhibition.

183 hibition of CDK9 by small interfering RNA or CDK9 inhibitor functionally suppressed RNA transcription

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

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

186 We determined that this compound is a potent CDK9 inhibitor with a previously uncharacterized scaffol

187 ion of early elongation using the reversible CDK9 inhibitor, 5,6-dichlorobenzimidazole 1-beta-D-ribof

188 ents was responsible for re-sensitization to CDK9 inhibitor, but not MCL1 inhibitor.

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

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

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

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

193 with regard to the development of selective CDK9 inhibitors.

194 in disease severity following treatment with CDK9 inhibitors.

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

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

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

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

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

200 Our studies demonstrate that CDK9 is present in distinct mTOR-like (CTOR) complexes i

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

202 andem SH2 domain, and here we show that Bur1/Cdk9 is the kinase responsible for these modifications i

203 Cyclin-dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic targe

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

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

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

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

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

209 ning progenitors, mutant embryos lacking the CDK9 kinase component of P-TEFb exhibit a surfeit of NC

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

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

212 bstrate for threonine phosphorylation by the Cdk9 kinase.

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

214 We found that cdk9 localization to the viral transcriptosomes requires

215 1-beta-D-ribofuranosylbenzimidazole) allowed cdk9 localization to the viral transcriptosomes.

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

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

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

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

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

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

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

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

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

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

226 on factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (R

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

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

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

230 Phosphorylation by Cdk9 or phosphomimetic substitution of its target residu

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

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

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

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

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

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

237 Conversely, CDK9 phosphorylates BRD4 enhancing its CTD kinase activi

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

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

240 CDK9 plays a crucial role in transcription regulation; s

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

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

243 se (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation.

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

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

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

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

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

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

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

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

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

253 4 is required for cyclin-dependent kinase 9 (CDK9) recruitment and phospho-Ser 2 carboxy-terminal dom

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

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

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

257 In addition, increased CDK9 significantly correlated with poor patient prognosi

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

259 CDK9 specific inhibitors may be a potential alternative

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

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

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

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

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

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

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

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

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

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

270 c), activation of cyclin-dependent kinase 9 (CDK9)-that phosphorylates NELF and the carboxyl terminal

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

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

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

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

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

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

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

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

279 lood, Beauchamp et al reveal that the kinase CDK9, typically associated with transcriptional elongati

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 CDK9 was highly expressed in human ovarian cancer cell l

286 ells rather than in T cells and that whereas CDK9 was involved in activating HIV-1 by I-BET151 in bot

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

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

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