ライフサイエンスコーパス: CDK6

1 nslated region of cyclin-dependent kinase 6 (CDK6).

2 yclin-dependent kinase (e.g., cdk2, cdk4, or cdk6).

3 potent and selective inhibitors of CDK4 and CDK6.

4 t least partially, through the activation of Cdk6.

5 ification or overexpression of cyclin Ds and Cdk6.

6 e partially rescued by ectopic expression of CDK6.

7 xpected, and also cyclin-dependent kinase 6, CDK6.

8 for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6.

9 4b) or p16(Ink4a) or upregulation of CDK4 or CDK6.

10 lated cell-cycle progression genes including Cdk6.

11 umors, including met, cyclinD2, slc45a3, and cdk6.

12 representative compounds bound to monomeric CDK6.

13 clin-dependent kinases CDK1, CDK2, CDK4, and CDK6.

14 ing phosphorylation of CDK1, CDK2, CDK4, and CDK6.

15 g to CDK4 but remains able to associate with CDK6.

16 hat lead to sterical clashes in CDK2 but not CDK6.

17 n of D-cyclin-dependent Rb kinases, CDK4 and CDK6.

18 rget genes including SIRT1, BCL2, c-MET, and CDK6.

19 umour regression upon inhibition of CDK4 and CDK6.

20 the expression of cyclin D2, cyclin D3, and CDK6.

21 HSC subsets through the expression level of CDK6.

22 ession in association with downregulation of CDK6.

23 cl-xL, whereas miR-491-3p targets IGFBP2 and CDK6.

24 feration by suppressing Cyclin D1, CDK4, and CDK6 accumulation.

25 Here we show that Cdk7 is a Cdk4- and Cdk6-activating kinase in human cells, required to maint

26 novel downstream target of NFATc1-cyclin D1/CDK6 activity in mediating vascular wall remodeling foll

27 f cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 activity leading to pRb hypophosphorylation and cel

28 nt, NFATc1-mediated cyclin D1 expression and CDK6 activity mediate this effect.

29 astoma tumor suppressor is inactivated, CDK4/CDK6 activity needs to be inhibited in order for cells t

30 ail to reduce the activity of cyclin D3-cdk4/cdk6 after partial hepatectomy, leading to high levels o

31 and found that mice expressing a kinase-dead Cdk6 allele (Cdk6(K43M)) had a pronounced reduction in t

32 1) phase-specific cyclin-dependent kinase 6 (CDK6) also blocks erythroid differentiation.

33 c melanoma cells results in higher levels of CDK6 and a more significant response to CDK4/6 inhibitor

34 howed that miR-491-5p directly targets EGFR, CDK6 and Bcl-xL, whereas miR-491-3p targets IGFBP2 and C

35 le in Ph(+) ALL, pharmacologic inhibition of CDK6 and BCL2 markedly suppressed proliferation, colony

36 regulation on S-phase entry, suggesting that CDK6 and CDC25A are downstream cell cycle effectors of N

37 CDC25A expression in hESCs suggest that both CDK6 and CDC25A are involved in S-phase regulation.

38 Decreased CDK6 and CDC25A expression in hESCs suggest that both CD

39 of NANOG binds to the regulatory regions of CDK6 and CDC25A genes under normal physiological conditi

40 cent proline (P173), which is not present in CDK6 and CDK1/2.

41 Under these conditions, CDK6 and CDK2 kinase activities were decreased, whereas

42 yclin E proteins co-immunoprecipitating with cdk6 and cdk2, respectively.

43 MCP1 induced cyclin D1 expression as well as CDK6 and CDK4 activities, and these effects were depende

44 ling, decreased the protein levels of ITGB1, CDK6 and cyclin D1 and caused reduced expression of anti

45 ox withdrawal resulted in a reversal of both cdk6 and cyclin D1 expression as well as beta-cell proli

46 o marked dose- and time-related increases in cdk6 and cyclin D1, accompanied by a 20-fold increase in

47 an beta-cells from T2D donors in response to cdk6 and cyclin D3 is indeed dramatically impaired.

48 Cdk6 and cyclin D3 were used to drive human beta-cell pr

49 howed preferential complex formation between CDK6 and cyclin D3, suggesting that this particular comp

50 cells induces cell cycle arrest by targeting CDK6 and decreases the levels of phosphorylated-Rb1 and

51 ivates the cyclin-dependent kinases CDK4 and CDK6 and drives cell proliferation.

52 potecan is associated with reduced levels of CDK6 and HIF-1alpha, as well as pronounced changes in ce

53 were identified, amongst which STAT3, PKM2, CDK6 and LASP-1 showed induction of specific phosphoryla

54 irmed using green fluorescent protein-tagged cdk6 and live cell imaging.

55 epleted NSCLC cells as well as the levels of CDK6 and NANOS1 expression in these cells.

56 usly reported functions in other cell types, CDK6 and NANOS1 were required for the proliferation and

57 le in hypertension of several genes, such as CDK6 and NUCB2.

58 ath, downregulation of cell cycle-associated Cdk6 and of cyclin D, E, and A proteins, and downregulat

59 However, nuclear localization of CDK6 and P27 was markedly enhanced in CHI-D beta-cells c

60 liferation and enhanced activity of Cdk4 and Cdk6 and phosphorylation of Rb protein.

61 ionship between control of the cell cycle by CDK6 and SAMHD1 activity, which is important for replica

62 Although CDK4 and CDK6 and their INK4-insensitive variants can extend the

63 inase N1 (PKN1) downstream of Rac1-cyclin D1/CDK6 and upstream of CDK4-PAK1 in the p115 RhoGEF-Rac1-N

64 The cyclin-dependent kinase 6 (CDK6) and CDK4 have redundant functions in regulating ce

65 levels of cell cycle-associated genes (e.g. CDK6) and cell invasion-related genes (e.g. NANOS1); the

66 molecules such as cyclin-dependent kinase 6 (cdk6) and cyclin D1, but their continuous overexpression

67 own-regulation of cyclin-dependent kinase 6 (CDK6) and integrin beta1 (ITGB1), which were functionall

68 eam activation of cyclin-dependent kinase 6 (Cdk6) and MycNol3(-/-) MPN Thy1(+)LSK cells share signif

69 rgeting of HMGA2, cyclin-dependent kinase 6 (CDK6), and other predicted miR-33b targets.

70 Human beta-cells contain abundant cdk4, cdk6, and cyclin D3, but variable amounts of cyclin D1.

71 egulation of p27 and downregulation of CDK4, CDK6, and cyclin D3.

72 eration-specific antigen, Ki67, altered p21, cdk6, and cyclinD activity and an increased apoptotic-pr

73 by increased expression of cyclin D2, CDK4, CDK6, and phospho-retinoblastoma protein.

74 These results suggest that CDK6 antagonists may be a promising therapeutic approach

75 Inhibitors of CDK4 and CDK6 are currently being tested in clinical trials for p

76 ion of the cyclin-dependent kinases CDK4 and CDK6 are essential and sufficient to impair senescence i

77 Cyclin-dependent kinase (CDK)4 and CDK6 are frequently overexpressed or hyperactivated in h

78 Cdk4 and Cdk6 are inhibited by INK4 proteins, which exert tumor-s

79 These observations suggest that CDK4 and CDK6 are not functionally redundant and underscore the i

80 Cdk4 and Cdk6 are related protein kinases that bind d-type cyclin

81 ssociated cyclin-dependent kinases (CDK4 and CDK6) are components of the core cell cycle machinery th

82 ciated with high levels of CDK6, pointing to CDK6 as a direct transcriptional target of the Hh pathwa

83 This role of CDK6 as a downstream mediator of Notch identifies CDK6 k

84 d comprehensive genomic analyses to identify CDK6 as a GBM oncogene that is required for proliferatio

85 acke et al identify the cell-cycle regulator CDK6 as a promising new target in mixed lineage leukemia

86 pment and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid

87 selective and reversible inhibition of CDK4/CDK6 as an effective means to enhance Ara-C killing of A

88 Our findings define CDK6 as an important regulator of stem cell activation a

89 These data identify CDK6 as critical effector of MLL fusions in leukemogenes

90 nscriptome, which includes oncogenes MYC and CDK6 as direct targets.

91 ntified cyclin D-dependent kinases, CDK4 and CDK6, as the major oncogenic drivers among members of th

92 levels of the clients ERBB2, CRAF, CDK4 and CDK6, as well as phosphorylated AKT.

93 clin-dependent kinases (CDK) (CDK2, CDK4 and CDK6) at variable levels.

94 tinib-resistant MCL cells, which overexpress CDK6, BCL2, Bcl-xL, XIAP, and AKT, but lack ibrutinib re

95 Egr1 knock-down in Cdk6(-/-) BCR-ABL(p210+) LSKs significantly enhances the

96 Four of these genes (CDCA7L, CDK6, BTG1 and SAMD3) were tested for RAR and AR binding

97 L cells exhibited a specific requirement for CDK6 but not CDK4 expression, most likely because, in th

98 bed to the transcriptional activity of CDK6: CDK6 but not its functional homolog CDK4 is found at the

99 tionally reliant on the cell-cycle regulator CDK6, but not its functional homolog CDK4, and that the

100 of ClC-3 siRNA on the expression of CDK4 and CDK6, but not on that of cyclin D1, indicating the requi

101 tion of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of function or loss of inhibition is common

102 be ascribed to transcriptional activation of CDK6 by mutant MLL.

103 Inhibition of Cdk4/Cdk6 by p18(INK4c) (p18) is pivotal for generation of no

104 In vivo, timely inhibition of CDK4/CDK6 by PD 0332991 and release profoundly suppresses tum

105 bryonic development-related genes, including CDK6, c-MYC, HDAC1 and BCL-2, are targets of miR-449b.

106 449b could regulate the expression levels of CDK6, c-MYC, HDAC1 and BCL-2.

107 Here we show that CDK4 and CDK6 can extend the life span of HDFs that have inactiva

108 These include Plcgamma2, Cdk6, CD25, Tox, Gadd45a, Gadd45b, Gfi1, Gfi1b, Socs1, S

109 esponding cyclin-dependent kinases (CDK4 and CDK6 [CDK4/6]).

110 c1 led to decreased cyclin D1 expression and CDK6, CDK4, and Pak1 activities, resulting in reduced ne

111 tion abrogated MCP1-induced NFATc1-cyclin D1-CDK6-CDK4-Pak1 signaling and, thereby, decreased HASMC F

112 or MCP-1-induced activation of the cyclin D1-CDK6-CDK4-Pak1 signaling axis, affecting their migration

113 ascribed to the transcriptional activity of CDK6: CDK6 but not its functional homolog CDK4 is found

114 isms in the CCNB1, CCND1, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, and CDKN2A genes were genotyped an

115 trol-CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, and CDKN2D

116 target for phosphorylation by cyclin D3-cdk4/cdk6 complexes in differentiated liver cells and in diff

117 tumours expressing high levels of cyclin D3-CDK6 complexes.

118 t also functions as an activator of cyclin D-Cdk6 complexes.

119 e the expression of active cyclin D/Cdk4 and Cdk6 complexes; it also induced the phosphorylation of R

120 Thus, SUMO1-CDK6 conjugation constitutes a mechanism of cell cycle c

121 Our observations reveal that Cdk4 and Cdk6 cooperate in hematopoietic tumor development and su

122 s sufficient to protect kinase clients CDK4, CDK6, CRAF and ERBB2 from depletion induced by silencing

123 Two genes, CDK6 (cyclin-dependent kinase 6) and XRCC1, were signifi

124 MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expr

125 yclin-dependent kinase 4 (Cdk4)-cyclin D1 or Cdk6-cyclin D2 precedes proliferation of bone marrow mye

126 End points were cdk6/cyclin D1 expression and human beta-cell proliferat

127 ses in human beta-cell replication, with the cdk6/cyclin D3 combination being the most robust (15% ve

128 pulate upon competitive transplantation, and Cdk6-deficient mice are significantly more susceptible t

129 Cdk6-deficient mice show pronounced thymic atrophy due t

130 Furthermore, CDK6-deficient mice were resistant to lymphomagenesis in

131 Lys 147 and inhibits the ubiquitin-mediated CDK6 degradation.

132 tivation in a sustained and NFATc1-cyclin D1/CDK6-dependent manner.

133 he preferential growth inhibition induced by CDK6 depletion is mediated through enhanced myeloid diff

134 colonies, underlining the importance of the CDK6-Egr1 axis.

135 CDK6 essentiality is also evident in AML cells harboring

136 ion of CDK6 resulted in a marked increase in CDK6 expression and reduced response of the CDK4/6 targe

137 Here, we show that microRNA-200a decreases CDK6 expression and thus reduces the response of CDK4/6

138 y, the context-dependent effects of lowering CDK6 expression are closely phenocopied by a small-molec

139 Enforced CDK6 expression in LT-HSCs shortens quiescence exit and

140 B cells and that the v-Abl kinase stimulates Cdk6 expression via an extracellular signal-regulated ki

141 lerates cell cycle progression by activating CDK6 expression via the c-JUN transcription factor.

142 2 binding to the Cdk6 promoter and activated Cdk6 expression, thereby promoting uncontrolled cell pro

143 ssays indicated that Pax6 directly represses Cdk6 expression.

144 nhibitory effects of ClC-3 siRNA on CDK4 and CDK6 expression.

145 which appeared to be activated downstream of CDK6, formed a complex with Pak1 in response to MCP1.

146 f p18(Ink4c) (p18), an inhibitor of CDK4 and CDK6, functionally inactivates the RB pathway, stimulate

147 U.1 directly stimulates transcription of the cdk6 gene in both normal erythroid progenitors and eryth

148 variance explained = 1.90%) and one over the CDK6 gene on chromosome 7 (rs445, p value = 6.03 x 10(-1

149 s, we generated transgenic mice carrying the CDK6 gene under the keratin 5 promoter (K5CDK6).

150 The G1 cell-cycle kinase CDK6 has long been thought of as a redundant homolog of

151 Knockouts of Cdk2, Cdk3, Cdk4, or Cdk6 have resulted in viable mice, but the in vivo funct

152 Inhibition of CDK4 and CDK6 (hereafter CDK4/6) in vivo increases PD-L1 protein

153 matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights i

154 CDK4 and CDK6, however, may be at least as important as enzymes f

155 ppears normal under steady-state conditions, Cdk6(-/-) HSCs do not efficiently repopulate upon compet

156 e resulted in enhanced expression of Myc and Cdk6 in BM.

157 h CDK4 in lung cancer, and low DLC1 and high CDK6 in colon cancer.

158 Targeting CDK4/CDK6 in combination with cytotoxic killing therefore rep

159 To determine the role of CDK6 in development and tumorigenesis, we generated and

160 , we suggest that the aberrant activation of Cdk6 in E47-deficient T lineage cells contributes to the

161 To study the role of CDK6 in epithelial growth and tumorigenesis, we generate

162 We describe a novel role for CDK6 in hematopoietic and leukemic stem cells (hematopoi

163 and S424 are also phosphorylated by cdk1 or cdk6 in hematopoietic cells.

164 opose that measuring the levels of cyclin D3-CDK6 in human cancers might help to identify tumour subs

165 Genetic or pharmacological inhibition of CDK6 in mice repressed the growth of Hh-associated medul

166 hese results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumor

167 of cyclin D3 also results in mobilization of cdk6 in nuclei of infected cells.

168 d by down-regulation of cyclin D1, cdk4, and cdk6 in rap1GAP-transfected SCC cells.

169 Reversible inhibition of CDK4/CDK6 in sequential combination therapy thus represents a

170 tic tumor development and suggest a role for Cdk6 in sequestering INK4 proteins away from Cdk4.

171 conformational differences between CDK2 and CDK6 in the hinge region are contributing to the inhibit

172 To mechanistically dissect the role of CDK6 in thymocyte development, we generated and analyzed

173 These functions point to a role of CDK6 in tissue homeostasis and differentiation that is p

174 Inhibition of cyclin D3-CDK6 in tumour cells reduces flow through the PPP and se

175 by analyzing mutants of the KSHV-cyclin and Cdk6 in vitro as well as in U2OS cells.

176 the functional role of one of these targets, CDK6, in medulloblastoma.

177 CDK6, in neutrophils, is required for clearance of the f

178 nduction of pG1 and pG1-S by reversible CDK4/CDK6 inhibition further augments tumor-specific bortezom

179 of prolonged early-G(1) arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G(1) and

180 CDK4/CDK6 inhibition in vitro and in tumors in mice caused G1

181 are closely phenocopied by a small-molecule CDK6 inhibitor currently in clinical development.

182 OMA-3 study, the combination of the CDK4 and CDK6 inhibitor palbociclib and fulvestrant was associate

183 The selective CDK4 and CDK6 inhibitor palbociclib inhibits growth and induces s

184 e selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD0332991 inhibits growth and induces sen

185 Novel small molecule CDK4/CDK6 inhibitor PD0332991 profoundly suppressed--at low n

186 cell death, suggesting a potential role for CDK6 inhibitors in the treatment of STI571-resistant CML

187 mains a reliable readout for effects of CDK4/CDK6 inhibitors on cell proliferation.

188 lly, immunoprecipitation studies showed that CDK6 is a major binding partner for cyclin D3, whereas C

189 CDK6 is also a substrate of ubiquitin; however, CDK6 SUM

190 CDK6 is an oncogenic kinase regulating the cell cycle.

191 CDK6 is directly involved in transcription in tumor cell

192 Here we show that CDK6 is modified by small ubiquitin-like modifier-1 (SUM

193 h receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, prolifera

194 CDK6 is thus a new molecule involved in the control of m

195 Cyclin-dependent kinase-6 (CDK6) is required for early thymocyte development and tu

196 n of the G(1) proteins, cyclin D3, CDK4, and CDK6, is Notch-dependent both in vitro and in vivo, and

197 Further, knockout of CD25 in Cdk6(K43M) mice rescued most defects observed in young m

198 t mice expressing a kinase-dead Cdk6 allele (Cdk6(K43M)) had a pronounced reduction in thymocytes and

199 as a downstream mediator of Notch identifies CDK6 kinase activity as a potential therapeutic target i

200 Our mechanistic studies demonstrate that CDK6 kinase activity contributes to Notch signaling beca

201 icancer therapies based on the inhibition of CDK6 kinase activity fail to take into account its kinas

202 ese results illustrate an important role for CDK6 kinase activity in thymocyte development that opera

203 tributes to Notch signaling because inactive CDK6 kinase disrupts Notch-dependent survival, prolifera

204 nografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic ac

205 al were found to harbor amplification of the CDK6 kinase.

206 Although cyclin D3-cdk4/cdk6 kinases are involved in the promotion of growth, th

207 The activity of Cdk6.KSHV-cyclin complexes was investigated here by anal

208 R-6883-5p or miR-149* downregulated CDK4 and CDK6 levels in human colorectal cancer cells.

209 ip1) and down-regulation of cyclin B1, CDC2, CDK6, MCM4, and retinoblastoma.

210 se assays showed that p300 directly inhibits cdk6-mediated RB phosphorylation, suggesting p300 acts i

211 Multiple shRNAs against CDK6, MET, and MAP2K1 (also known as MEK1) preferentiall

212 ith BCR-ABL(p210+)-infected bone marrow from Cdk6(-/-) mice fails to induce disease, although recipie

213 m, we generated knock-in mice that express a Cdk6 mutant (Cdk6 R31C) insensitive to INK4-mediated inh

214 in alterations and cell-cycle-gene (CDK4 and CDK6) mutations.

215 Overexpression of CDK6 or CDC25A alone can rescue the impact of NANOG down

216 tion are mitigated by the down-regulation of CDK6 or CDC25A alone.

217 line (Dox)-inducible adenoviruses expressing cdk6 or cyclin D1.

218 Depletion of NFATc1, cyclin D1, CDK6, or CDK4 levels attenuated MCP1-induced Pak1 phosph

219 erts its function through activation of CDK4/CDK6, our results in primary MCL cells indicate that dow

220 CDK6 overexpression also triggered keratinocyte apoptosi

221 Unexpectedly, cyclin D3 and cdk6 overexpression drives human beta-cell replication m

222 Not only did CDK6 overexpression mediate resistance to CDK4/6 inhibit

223 Unexpectedly, CDK6 overexpression results in decreased skin tumor deve

224 roliferation; these effects are recovered by CDK6 overexpression.

225 tients, including compounds that target CDK4/CDK6 (palbociclib, ribociclib, and abemaciclib), aurora

226 ll, Kollmann and colleagues demonstrate that CDK6 performs a kinase-independent transcriptional funct

227 ugh a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1.

228 ined druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient

229 AK1 in the p115 RhoGEF-Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling axis is involved in the mo

230 ed MCP1- or BI-induced Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling, which, as we reported pre

231 in vivo by modulating Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling.

232 udies provide in vivo evidence that CDK4 and CDK6 play a similar role as a mediator of keratinocyte p

233 ets and as effectively as the combination of cdk6 plus a D-cyclin.

234 signaling was associated with high levels of CDK6, pointing to CDK6 as a direct transcriptional targe

235 ntaining 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1

236 g beta-cells contained nuclear cyclin D3 and cdk6, proliferation generally did not occur in beta-cell

237 Hh signaling induced GLI2 binding to the Cdk6 promoter and activated Cdk6 expression, thereby pro

238 We found that forced expression of Cdk6 promotes continued cell division and decreased apop

239 Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpress

240 hermore, we demonstrate miR-29 inhibition of CDK6 protein and mRNA levels by direct binding to 3'-unt

241 ulloblastoma cells and Notch-1, Notch-2, and CDK6 protein expressions in glioma cells.

242 ST)-HSCs are also quiescent but contain high CDK6 protein levels that permit rapid cell cycle entry u

243 in CDK2, but no change in p53, p57, CDK4, or CDK6 protein.

244 LT-HSCs lack CDK6 protein.

245 R and AR binding and two of them (CDCA7L and CDK6) proved to be antagonistically regulated by androge

246 A single molecule, cdk6, proved to be capable of driving human beta-cell re

247 Cdk6(R/R) mice display altered development of the hemato

248 Cdk4, whereas cells harboring Cdk4 R24C and Cdk6 R31C are fully insensitive to INK4 inhibitors, resu

249 In BCR-ABL-transformed hematopoietic cells, Cdk6 R31C causes increased binding of p16(INK4a) to wild

250 Unexpectedly, Cdk6 R31C impairs the potential of hematopoietic progeni

251 ed knock-in mice that express a Cdk6 mutant (Cdk6 R31C) insensitive to INK4-mediated inhibition.

252 expressing the INK4-insensitive, hyperactive Cdk6(R31C) allele displayed excess proliferation in LSK

253 Cyclin D dependent kinases (CDK4 and CDK6) regulate entry into S phase of the cell cycle and

254 There CDK6 regulates transcription in a kinase-dependent manne

255 rn mediates CDK6 SUMOylation during mitosis; CDK6 remains SUMOylated in G1 phase and drives the cell

256 Knockdown of CDK6 restored drug sensitivity, while enforced overexpre

257 Amplification of CDK6 resulted in a marked increase in CDK6 expression an

258 nd cyclin-dependent kinase 4 (cdk4), but not cdk6, resulting in an impaired downstream signaling with

259 s increased in old livers and activates cdk4/cdk6, resulting in stabilization of the C/EBPalpha-Brm c

260 Inhibition of CDK4/CDK6 revealed proteasome-mediated Ki-67 degradation in G

261 Additional work further confirmed CDK6, RICTOR, and CTSB (cathepsin B) as targets of miR-2

262 0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) o

263 erentiation that is partially independent of CDK6's kinase activity and is not shared with CDK4.

264 on in an attempt to link the new findings on CDK6's transcriptional activity to cell-cycle progressio

265 rylation of Rb protein at both CDK2 and CDK4/CDK6 sites were significantly increased in normal bronch

266 Associations for CDK6 SNPs were stronger in CDKN2A mutation-positive fami

267 Cyclin D3-cdk4/cdk6 specifically phosphorylate C/EBPalpha at Ser193 in

268 inhibitor of G1 cyclin Ds-dependent CDK4 and CDK6, stimulates mammary luminal progenitor cell prolife

269 ors of the cyclin-dependent kinases CDK4 and CDK6 substantially improve progression-free survival.

270 NK4A) activity depends on inhibition of CDK4/CDK6, suggesting that in cervical cancer cells where ret

271 6 is also a substrate of ubiquitin; however, CDK6 SUMOylation at Lys 216 blocks its ubiquitination at

272 ugating enzyme9 (UBC9) that in turn mediates CDK6 SUMOylation during mitosis; CDK6 remains SUMOylated

273 modifier-1 (SUMO1) in glioblastoma, and that CDK6 SUMOylation stabilizes the protein and drives the c

274 In this paper, we show that cyclin D3-cdk4/cdk6 supports the ability of C/EBPalpha to inhibit liver

275 Most importantly, a single molecule, cdk6, supports robust human beta-cell proliferation and

276 cells, presumably because they express more CDK6 than primary fibroblasts.

277 up-regulation of the expression of CDK4 and CDK6 through suppression of p21 and p27 expression.

278 transcription at key genes (BCL2, C-MYC and CDK6) through the displacement of BRD3/4, PAFc and SEC c

279 Cyclin D3-CDK6, through its ability to link cell cycle and cell me

280 was unknown if Cdk7 also activates Cdk4 and Cdk6 to promote passage of the restriction (R) point, wh

281 review the literature on the contribution of CDK6 to transcription in an attempt to link the new find

282 rated to activate cyclin-dependent kinase 6 (Cdk6) to induce the phosphorylation of various cell cycl

283 gakaryocyte differentiation, and of CDK4 and CDK6, to inhibit the G(1)/S transition.

284 LL cell lines, ectopic expression of CDK4 or CDK6 together with cyclin D3 shows partial rescue from g

285 ranscription factor E2A negatively regulates Cdk6 transcription in leukemic pro-B cells and that the

286 Thus, differential expression of CDK6 underlies heterogeneity in stem cell quiescence sta

287 -regulated by nuclear p44) and cyclin D2 and CDK6 (up-regulated by cytoplasmic p44).

288 loci (PKN, FN1, UGT1A1, PPARG, DMDGH, PPARD, CDK6, VPS13B, GAD2, GAB2, APOH and NPC1) for low-density

289 Dynamic cytoplasmic-nuclear trafficking of cdk6 was confirmed using green fluorescent protein-tagge

290 Inverse correlation between miR-29 and CDK6 was observed in MCL.

291 ession, most likely because, in these cells, CDK6 was predominantly localized in the nucleus, whereas

292 ensitivity, while enforced overexpression of CDK6 was sufficient to mediate drug resistance.

293 tors of cyclin-dependent kinase 4 (CDK4) and CDK6, we have demonstrated that selective cellular quies

294 selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proli

295 rocycling proteins CYCLIN E2, CYCLIN D2, and CDK6 were all reduced.

296 Levels of MYB and CDK6 were highly correlated in adult Ph(+) ALL (P = 0.00

297 nd -D3 and cyclin-dependent kinases CDK4 and CDK6 were significantly lower, whereas the protein level

298 Expression levels of phosphorylated AKT and CDK6 were significantly reduced in the cancers developin

299 We find that activation of HSCs requires CDK6, which interferes with the transcription of key reg

300 escribe here two complex structures of human CDK6 with a very specific kinase inhibitor, PD0332991, w

301 By selective inhibition of CDK4/CDK6 with PD 0332991, which leads to early G1 arrest and