ライフサイエンスコーパス: CDK6

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

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

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

4 HSC subsets through the expression level of CDK6.

5 ession in association with downregulation of CDK6.

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

7 t least partially, through the activation of Cdk6.

8 ification or overexpression of cyclin Ds and Cdk6.

9 e partially rescued by ectopic expression of CDK6.

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

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

12 4b) or p16(Ink4a) or upregulation of CDK4 or CDK6.

13 lated cell-cycle progression genes including Cdk6.

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

15 representative compounds bound to monomeric CDK6.

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

17 ator of resistance to inhibition of CDK4 and CDK6.

18 4/6, or selectively degrading either CDK4 or CDK6.

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

20 umour regression upon inhibition of CDK4 and CDK6.

21 potent and selective inhibitors of CDK4 and CDK6.

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

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

24 kn2ab-deficient cell lines primarily through CDK6 activation.

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

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

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

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

29 The absence of Cdk6 ameliorates clinical symptoms and prolongs survival

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

56 iven by cyclin-dependent kinase 4 (CDK4) and CDK6 and the methyltransferase EZH2 as a valid target fo

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

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

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

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

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

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

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

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

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

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

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

68 rectly targeting EMT-promoting factors ZEB1, cdk6, and Snail.

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

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

71 ibitors of cyclin-dependent kinases CDK4 and CDK6 are effective in some cancer types and are currentl

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

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

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

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

76 gesting that the growth-promoting effects of CDK6 are, in part, kinase-independent in Ph+ ALL.

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

78 These findings identify CDK6 as a conserved, critical direct target of NUP98-fus

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

80 chronic lymphocytic leukemia, and supported CDK6 as a disease-specific target in acute myeloid leuke

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

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

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

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

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

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

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

88 identifies cyclin-dependent kinases CDK4 and CDK6 as regulators of metastasis through distinct signal

89 f inducing selective degradation of CDK4 and CDK6 as tools to pharmacologically dissect their distinc

90 CDK7 and CDK9) and cell cycle CDKs (CDK4 and CDK6) as well.

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

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

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

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

95 a novel regulatory axis of miR-934/UBE2N of CDK6 but also provides data suggesting that miR-934 and

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

97 Inhibition of CDK6 but not CDK4 resulted in defective DNA repair and i

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 nstead primarily targeted monomeric CDK4 and CDK6 (CDK4/6) in breast tumor cells.

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

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

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

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

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

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

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

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

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

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

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

119 een treatment and expression levels of CDK4, CDK6, cyclin D1, and RB1.

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

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

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

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

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

125 Treatment with the CDK6-degrading PROTAC YX-2-107 markedly suppressed leuke

126 esents an effective strategy to exploit the "CDK6 dependence" of Ph+ ALL and, perhaps, of other hemat

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

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

129 Multiple CDK6 DNA replication/repair genes were not only associat

130 CRISPR-based genomic deletion of CDK6 efficiently blocked tumor formation and progression

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

132 is-targeting chimeras (PROTACs) that inhibit CDK6 enzymatic activity in vitro, promote the rapid and

133 date predicted resistance mutations in CDK4, CDK6, ERK2, EGFR and HER2.

134 CDK6 essentiality is also evident in AML cells harboring

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

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

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

138 ecular mechanisms concerning how to regulate CDK6 expression in BC remains unclear.

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

144 ssays indicated that Pax6 directly represses Cdk6 expression.

145 The cyclin-dependent kinases Cdk4 and Cdk6 form complexes with D-type cyclins to drive cell pr

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

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

148 Combining in vivo CRISPR-based CDK4 and CDK6 gene editing with pharmacologic inhibition approach

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

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

151 MDS2, PBX1, CYP1A2, VPRBP, WBP1L, CD28, and CDK6 genes), and prenatal smoking x DNAm interactions on

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

153 his context, multiple inhibitors of CDK4 and CDK6 have been developed, including three small molecule

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

155 such as cyclin-dependent kinase 4 (CDK4) and CDK6, have attracted considerable interest as potential

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

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

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

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

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

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

162 els, we defined clear functions for CDK4 and CDK6 in facilitating tumor growth and progression in met

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

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 We describe a critical role for CDK6 in MPN evolution.

167 y palbociclib, showing that the functions of CDK6 in MPN pathogenesis are largely kinase independent.

168 dings thus provide a rationale for targeting CDK6 in MPN.

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

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

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

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

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

177 Moreover, CDK4/CDK6 inhibition delays acquisition of resistance.

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 98-fusion AML was sensitive to pharmacologic CDK6 inhibition in vitro and in vivo.

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

183 This is borne out by the fact that a CDK6 inhibitor had been approved to treat several types

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

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

186 e to tamoxifen, fulvestrant and the CDK4 and CDK6 inhibitor palbociclib.

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

188 get of NUP98-fusion proteins, proposing CDK4/CDK6 inhibitors as a new rational treatment option for A

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

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

191 dicates that the anticancer activity of CDK4/CDK6 inhibitors results not only from their ability to b

192 Cs contained sensitizing events for CDK4 and CDK6 inhibitors, which were highly correlated with clini

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

194 CDK6 is an oncogenic kinase regulating the cell cycle.

195 CDK6 is directly involved in transcription in tumor cell

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

197 nhibition of the cell-cycle kinases CDK4 and CDK6 is now part of the standard treatment in advanced b

198 Expression of the cell cycle regulatory gene CDK6 is required for Philadelphia-positive (Ph+) acute l

199 eutic effects and whether targeting CDK4 and CDK6 is sufficient to reactivate RB pathway activity in

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

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

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

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

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

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

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

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

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

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

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

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

212 tic inflammatory cytokine signaling, whereas CDK6 mainly controlled DNA replication and repair proces

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

214 liferation-associated genes such as CCNA and CDK6 Moreover, repressive YAP-TEAD4 complexes containing

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

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

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 ve in myeloid development (eg, CD164, PROM1, CDK6, or MYC).

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

221 te the rapid and preferential degradation of CDK6 over CDK4 in Ph+ ALL cells, and markedly suppress S

222 CDK6 overexpression also triggered keratinocyte apoptosi

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

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

225 Unexpectedly, CDK6 overexpression results in decreased skin tumor deve

226 roliferation; these effects are recovered by CDK6 overexpression.

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

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

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

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

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

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

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

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

235 though the cyclin-dependent kinases CDK4 and CDK6 play fundamental roles in cancer, the specific path

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

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

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

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

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

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

242 tenuated CDK6 protein degradation and led to CDK6 protein accumulation as well as the promotion of BC

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

244 rotein expression; this, in turn, attenuated CDK6 protein degradation and led to CDK6 protein accumul

245 Inhibition of UBE2N-dependent CDK6 protein degradation by miR-934 promotes human bladd

246 th in vivo; the outcomes were accompanied by CDK6 protein down-regulation and G(0)-G(1) cell cycle ar

247 The CDK6 protein interferes with 3 hallmarks of disease: bes

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

249 LT-HSCs lack CDK6 protein.

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

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

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

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

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

255 Unexpectedly, Cdk6 R31C impairs the potential of hematopoietic progeni

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

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

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

259 S-phase cells concomitant with inhibition of CDK6-regulated phospho-RB and FOXM1 expression.

260 There CDK6 regulates transcription in a kinase-dependent manne

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

262 Knockdown of CDK6 restored drug sensitivity, while enforced overexpre

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

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

265 Moreover, overexpression of CDK6 reversed the inhibition of BC cell growth induced b

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

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

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

269 they suggest that treatment of Ph+ ALL with CDK6-selective PROTACs would spare a high proportion of

270 Loss of CDK6 severely attenuated NUP98-fusion-driven leukemogene

271 Moreover, CDK6 silencing is more effective than treatment with the

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

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

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

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

276 6 is also a substrate of ubiquitin; however, CDK6 SUMOylation at Lys 216 blocks its ubiquitination at

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

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

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

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

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

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

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

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

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

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

289 + normal hematopoietic progenitors, although CDK6 was efficiently degraded.

290 Among those, CDK6 was highly expressed in murine and human AML sample

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

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

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

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

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

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

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

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

301 provide "proof of principle" that targeting CDK6 with PROTACs that inhibit its enzymatic activity an