ライフサイエンスコーパス: cyclin-dependent kinase 4

1 tinoblastoma kinase activity associated with cyclin-dependent kinase 4.

2 products: p16, alternate reading frame, and cyclin-dependent kinase 4.

3 Entry into the cell cycle is mediated by cyclin-dependent kinase 4/6 (CDK4/6) activation, followe

4 EGFR-amplified tumours and a combination of cyclin-dependent kinase 4/6 (CDK4/6) and EGFR inhibitors

5 toma (Rb) protein [a target of the cyclin D1/cyclin-dependent kinase 4/6 (cdk4/6) holoenzyme] was del

6 rotoxicity, we show that the G1/S-regulating cyclin-dependent kinase 4/6 (CDK4/6) pathway is activate

7 (PD), an FDA-approved selective inhibitor of cyclin-dependent kinase 4/6 (CDK4/6), prevents radiation

8 D3 induction to specifically block cyclin D3-cyclin-dependent kinase 4/6 assembly.

9 ion phenotype was reversed by treatment with cyclin-dependent kinase 4/6 inhibitor, PD0332991/palboci

10 combination of a MEK inhibitor with PI3K or cyclin-dependent kinase 4/6 inhibitors.

11 Inactivation of both the pRb (pRb-cyclin D1/cyclin-dependent kinase 4/6-p16) and p53 (p53-p21(WAF1)-

12 s endogenous pRb phosphorylation by cyclin D-cyclin-dependent kinase 4/6.

13 rated previously that the cell cycle-related cyclin-dependent kinase 4/6/retinoblastoma protein pathw

14 cell cycle inhibitors Ink4a/b (inhibitors of cyclin-dependent kinase 4 A and B), the upregulation of

15 The p16(INK4a) protein inhibits cyclin-dependent kinase 4, a key regulator of progressio

16 ogen receptor by cyclin D1 is independent of cyclin-dependent kinase 4 activation.

17 ns by DNA damage identified Sertad1, a Cdk4 (cyclin-dependent kinase 4) activator.

18 ived of matrix contact, leading to a loss of cyclin-dependent kinase 4 activity and accumulation of h

19 Additionally, cyclin-dependent kinase-4 activity was decreased in asso

20 tibility genes in the human, Inhibitor A of [cyclin-dependent] kinase 4-alternative reading frame (IN

21 gene encoding the tumor suppressor inhibitor cyclin-dependent kinase 4/alternative reading frame (Ink

22 ient in the tumor suppressors inhibitor A of cyclin-dependent kinase 4/alternative reading frame resu

23 siRNA decreased the expression of cyclin D1, cyclin dependent kinase 4 and 6, and increased the expre

24 Finally, we show that the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor PD033

25 The p16 tumor suppressor specifically blocks cyclin-dependent kinase 4 and 6 activity.

26 the levels of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 and associated cyclins A, E, a

27 LPTs failed to upregulate cyclin-dependent kinase 4 and cyclin D3, but Rb phosphor

28 as the associated cyclin-dependent kinases, cyclin-dependent kinase 4 and cyclin-dependent kinase 6.

29 ssociated with binding of the p16 protein to cyclin-dependent kinase 4 and dephosphorylation of pRb.

30 ell division is regulated by the activity of cyclin-dependent kinase 4 and its obligate activating pa

31 two important regulators of the cell cycle, cyclin-dependent kinase-4 and its inhibitor p16, are inc

32 Consequently, cyclin D1 and cyclin-dependent kinases 4 and 2 (CDK4 and CDK2, respect

33 Both cyclin-dependent kinases 4 and 2 regained catalytic acti

34 se to homocysteine treatment, cyclin D1, and cyclin-dependent kinases 4 and 2 translocated to the nuc

35 hippocampal cell line, H19-7, that expresses cyclin-dependent kinases 4 and 5 (cdk4 and -5).

36 lity gene product, pRb, is down regulated by cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) whose k

37 assembly with their catalytic partners, the cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), into a

38 Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamenta

39 We identify cyclin-dependent kinases 4 and 6 (CDK4/6) as essential r

40 The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentia

41 Cyclin-dependent kinases 4 and 6 (CDK4/6) drive progress

42 Cyclin-dependent kinases 4 and 6 (CDK4/6) in complex wit

43 Activation of cyclin-dependent kinases 4 and 6 (cdk4/6) occurs in the

44 Acquired resistance to cyclin-dependent kinases 4 and 6 (CDK4/6) small-molecule

45 The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control t

46 The cyclin-dependent kinases 4 and 6 (Cdk4/6) that drive pro

47 A pharmacological approach to inhibition of cyclin-dependent kinases 4 and 6 (Cdk4/6) using highly s

48 rmation of enzymatically active complexes of cyclin-dependent kinases 4 and 6 (CDK4/6) with D-type cy

49 which ultimately leads to the activation of cyclin-dependent kinases 4 and 6 (Cdk4/6).

50 Cyclin-dependent kinases 4 and 6 are complexed with many

51 to and inhibiting the pRb kinase activity of cyclin-dependent kinases 4 and 6.

52 The tumor suppressor p16(INK4a) inhibits cyclin-dependent kinases 4 and 6.

53 to 9p21, p15 and p16, encode inhibitors for cyclin-dependent kinases 4 and 6.

54 -specific cyclins (cyclin A, D1, and D3) and cyclin-dependent kinases 4 and 6.

55 se p19(Arf)], designated INK4A (inhibitor of cyclin dependent kinase 4) and ARF (alternative reading

56 lies whom we tested for mutations in CDKN2A, cyclin-dependent kinase 4, and alternate reading frame.

57 Cyclin D1, cyclin-dependent kinase 4, and c-Myc were strongly incre

58 A complex with cyclin D3, cyclin-dependent kinase 4, and C/EBPalpha was observed a

59 other Hsp client proteins, including Raf-1, cyclin-dependent kinase 4, and epidermal growth factor r

60 e gene MTS1 encodes p16INK4, an inhibitor of cyclin-dependent kinase 4, and is frequently deleted, mu

61 Immunocomplex kinase assays with cyclin-dependent kinase 4 antiserum indicate that Tax bl

62 4-alternative reading frame (INK4A-ARF) and cyclin-dependent kinase 4, are involved in the regulatio

63 pe-like secondary and tertiary structure and cyclin-dependent kinase 4 binding activity.

64 esult of up-regulation of both cyclin D1 and cyclin-dependent kinase 4 by the HCV NS5A polypeptide.

65 Cyclin dependent kinase 4 (cdk4) activity is controlled

66 ermore, RAPA decreased the protein levels of cyclin dependent kinase 4 (CDK4) and increased the expre

67 2A (CDKN2A) gene and one of its targets, the cyclin dependent kinase 4 (CDK4) gene, have been identif

68 g the induction of cyclin D1 mRNA levels and cyclin dependent kinase 4 (CDK4)-cyclin D1 activity.

69 high-grade astrocytomas is amplification of cyclin dependent kinase-4 (CDK4).

70 ested cells in late G(1) prior to detectable cyclin-dependent kinase 4 (cdk4) activation.

71 The cyclin-dependent kinase 4 (CDK4) amplicon is frequently

72 Amplification of chromosome 12q13-q15 (Cyclin-dependent kinase 4 (CDK4) amplicon) is frequently

73 atic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an i

74 sion of cyclin D1, A2, and E, the persistent cyclin-dependent kinase 4 (CDK4) and CDK2 activities, an

75 This was shown by activation of cyclin-dependent kinase 4 (Cdk4) and Cdk2 and by the ind

76 cell cycle requires sequential activation of cyclin-dependent kinase 4 (cdk4) and cdk2, which phospho

77 Dysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of fun

78 Cyclin-dependent kinase 4 (Cdk4) and Cdk6, and later Cdk

79 urally distinct small molecule inhibitors of cyclin-dependent kinase 4 (CDK4) and CDK6, we have demon

80 the INK4 protein family specifically inhibit cyclin-dependent kinase 4 (cdk4) and cdk6-mediated phosp

81 al muscle myotubes (HSMMs), up-regulation of cyclin-dependent kinase 4 (CDK4) and concomitant phospho

82 ed cells requires expression and activity of cyclin-dependent kinase 4 (cdk4) and consequent de-repre

83 ses in the number of copies of the genes for cyclin-dependent kinase 4 (CDK4) and cyclin D1 (CCND1),

84 her with a decrease (up to 98%; P < 0.01) in cyclin-dependent kinase 4 (CDK4) and cyclin D1 protein l

85 We find that the cell cycle molecule cyclin-dependent kinase 4 (cdk4) and its downstream effe

86 elanoma cell lines with co-overexpression of cyclin-dependent kinase 4 (CDK4) and KIT.

87 d by expression of the nononcogenic proteins cyclin-dependent kinase 4 (Cdk4) and the catalytic compo

88 transfer (TR-FRET) assay for protein kinase cyclin-dependent kinase 4 (CDK4) and the identification

89 Cyclin D and cyclin-dependent kinase 4 (cdk4) are overexpressed in a

90 Network modeling pinpointed cyclin-dependent kinase 4 (CDK4) as a key driver of this

91 2D cells arrest in G(1) with active cyclin D-cyclin-dependent kinase 4 (Cdk4) but with inactive cycli

92 e that polyamines promote the translation of cyclin-dependent kinase 4 (CDK4) by the action of CUG-bi

93 Although cyclin D2-cyclin-dependent kinase 4 (cdk4) complexes mediate early

94 Although p27 associates with cyclin D-cyclin-dependent kinase 4 (cdk4) constitutively, whether

95 retinoblastoma protein phosphorylation, and cyclin-dependent kinase 4 (Cdk4) expression.

96 s of gene expression, we have identified the cyclin-dependent kinase 4 (CDK4) gene as a transcription

97 Among the genes regulated by Myc is the cyclin-dependent kinase 4 (CDK4) gene.

98 we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biolo

99 the involvement of the D-type cyclin partner cyclin-dependent kinase 4 (CDK4) in epithelial growth an

100 Overexpressing cyclin-dependent kinase 4 (Cdk4) in human epidermal kera

101 e expression of TGF-beta RII, cyclin D1, and cyclin-dependent kinase 4 (Cdk4) in Min/+ mouse intestin

102 nhibitor p16INK4A (P16) and gankyrin bind to cyclin-dependent kinase 4 (CDK4) in similar fashion, onl

103 To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have target

104 ransition, while it also binds and activates cyclin-dependent kinase 4 (CDK4) independent of the inhi

105 ent to promote cell cycle progression unless cyclin-dependent kinase 4 (cdk4) is also elevated, in th

106 ermore, chemical inhibition of the cyclin D1/cyclin-dependent kinase 4 (CDK4) kinase complex, used as

107 lexes which detectably interact neither with cyclin-dependent kinase 4 (CDK4) nor with DNA.

108 etically engineered to express cyclin D3 and cyclin-dependent kinase 4 (CDK4) phosphorylated GST fuse

109 uced an increase in cyclin D1, cyclin E, and cyclin-dependent kinase 4 (cdk4) protein levels in a bFG

110 The mechanism by which cyclin-dependent kinase 4 (CDK4) regulates cell cycle pr

111 assays, we showed that IkappaBalpha binds to cyclin-dependent kinase 4 (CDK4) specifically and inhibi

112 to target different immunogenic mutations in cyclin-dependent kinase 4 (CDK4) that naturally occur in

113 Here we show that MyoD can interact with cyclin-dependent kinase 4 (cdk4) through a conserved 15

114 synthesis of cyclin D1 and its assembly with cyclin-dependent kinase 4 (CDK4) to form an active compl

115 tion of cyclin-dependent kinase 2 (cdk2) and cyclin-dependent kinase 4 (cdk4) were delayed during pro

116 ociation of cell-cycle proteins p27(kip) and cyclin-dependent kinase 4 (CDK4) with Cdc42; and phospho

117 ated ERalpha, AIB1, pMAPK, HER-2, cyclin D1, cyclin-dependent kinase 4 (CDK4), and Bcl2 and up-regula

118 ulatory proteins, D-type and E-type cyclins, cyclin-dependent kinase 4 (Cdk4), and Cdk2.

119 increased expression of the early G1 kinase, cyclin-dependent kinase 4 (cdk4), and one of its regulat

120 lity of T cells to up-regulate cyclin D3 and cyclin-dependent kinase 4 (cdk4), but not cdk6, resultin

121 cer (HCC) with markedly increased cyclin D1, cyclin-dependent kinase 4 (Cdk4), c-Myc and MDM2 express

122 cell cycle regulatory cascade that includes cyclin-dependent kinase 4 (cdk4), cyclin D1, and pRb (re

123 Whereas cyclin D1b interacts with cyclin-dependent kinase 4 (CDK4), it is relatively ineff

124 immunofluorescent staining and expression of cyclin-dependent kinase 4 (Cdk4), p27(Kip1) (p27), phosp

125 udied function of cyclin D1 is activation of cyclin-dependent kinase 4 (CDK4), promoting progression

126 Although cyclin D1 binds and activates cyclin-dependent kinase 4 (Cdk4), thereby mediating acti

127 In this report, we identify the Drosophila cyclin-dependent kinase 4 (Cdk4), which exhibits embryon

128 Cyclin D1 formed complexes primarily with cyclin-dependent kinase 4 (cdk4), which were markedly ac

129 ort that in mice insulin activates cyclin D1-cyclin-dependent kinase 4 (Cdk4), which, in turn, increa

130 TRIP-Br1 is identical to the cyclin-dependent kinase 4 (cdk4)-binding protein p34(SEI

131 nknown, but mutually exclusive activation of cyclin-dependent kinase 4 (Cdk4)-cyclin D1 or Cdk6-cycli

132 The p16ink4a-cyclin D1/cyclin-dependent kinase 4 (Cdk4)-retinoblastoma (Rb) pat

133 e the phosphorylation of Rb, by binding with cyclin-dependent kinase 4 (CDK4).

134 thway negatively regulates the expression of cyclin-dependent kinase 4 (CDK4).

135 le the function was assayed by inhibition of cyclin-dependent kinase 4 (CDK4).

136 that operates during G1 phase by activating cyclin-dependent kinase 4 (Cdk4).

137 ilaggrin and downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4).

138 n that was mediated by the neo-expression of cyclin-dependent kinase 4 (CDK4).

139 in has been reported to be phosphorylated by cyclin-dependent kinase 4 (cdk4).

140 The selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD033299

141 des the p16 (encoded by the CDKN2A gene) and cyclin-dependent kinase 4 (cdk4, encoded by the CDK4 gen

142 sed cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4 (cdk4) activity.

143 n the aberrant region-specific expression of cyclin-dependent kinase-4 (cdk4) and -6 (cdk6), growth d

144 nhanced the kinase activity of the cyclin D1-cyclin-dependent kinase-4 (cdk4) complex.

145 us study, we reported that overexpression of cyclin-dependent kinase-4 (CDK4) in mouse epidermis resu

146 Newly synthesized cyclin D1 assembled with cyclin-dependent kinase-4 (CDK4) to form holoenzyme comp

147 Inhibition of the cell cycle kinase, cyclin-dependent kinase-4 (Cdk4), is expected to provide

148 rresting cells in the G1 phase by inhibiting cyclin-dependent kinases 4 (Cdk4) and 6 (Cdk6), thus pre

149 ts antitumor actions led to the inhibitor of cyclin-dependent kinase 4, CDKN2A.

150 An increase in cyclin D1/cyclin-dependent kinase 4 complex was also demonstrated

151 C12 myoblasts by transient activation of the cyclin-dependent kinase 4 complex, subsequent phosphoryl

152 KN2 encodes a specific inhibitor of cyclin D-cyclin-dependent kinase 4 complexes important in cell-cy

153 equestered by high levels of active cyclin D/cyclin-dependent kinase 4 complexes.

154 ich is involved in the assembly of cyclin D1/cyclin-dependent kinase-4 complexes, was increased by DH

155 is resistant to both CycE/cdk2 and Cyclin D/cyclin-dependent kinase 4 (CycD/cdk4).

156 xO activation were found to be inhibition of cyclin-dependent kinase 4, cyclin-dependent kinase 6, an

157 in the levels of the p16(INK4a), p27(KIP1), cyclin-dependent kinase 4, cyclin-dependent kinase 6, gl

158 se 4 proteins, and a concomitant decrease in cyclin-dependent kinase 4/cyclin D1 associated kinase ac

159 and p27 was increased while the activity of cyclin-dependent kinase 4 decreased.

160 ction depends on three cyclin D1 activities: cyclin-dependent kinase 4-dependent kinase activity, tit

161 ormation after transduction with telomerase, cyclin-dependent kinase 4, dominant-negative p53, and ac

162 ll cycle arrest in A431 cells is mediated by cyclin-dependent kinase 4 downregulation.

163 antigen overexpression and abnormalities in cyclin-dependent kinase 4, epidermal growth factor recep

164 The INK4 (inhibitor of cyclin-dependent kinase 4) family consists of four tumor

165 at proteins including the INK4 (inhibitor of cyclin-dependent kinase 4) family have been reported rec

166 blastoma protein and no amplification of the cyclin-dependent kinase 4 gene.

167 iated with DNA repair capacity for two hTERT/cyclin-dependent kinase 4, immortalized bronchial epithe

168 and activated Rb protein phosphorylation by cyclin-dependent kinase 4 in vitro and in vivo.

169 hat both an alternative EGFR inhibitor and a cyclin-dependent kinase 4 inhibitor led to significant i

170 se, but increased expression of inhibitor of cyclin dependent kinase 4 (INK4) family cell cycle inhib

171 hyperaccumulation of active cyclin D1.CDK4 (cyclin-dependent kinase 4) kinase.

172 esult that may be due to an effect of p16 on cyclin-dependent kinase 4 levels and IL-12 secretion by

173 ed with induction of the INK4 (inhibitors of cyclin dependent kinase 4) locus leading to cell-cycle a

174 D1 suggests that cyclin D1 or its associated cyclin-dependent kinase 4 may be useful targets in the t

175 Furthermore, induction of cyclin D and cyclin-dependent kinase 4 mRNA and protein was blocked u

176 hibitor, Gleevec, which blocked cyclin D and cyclin-dependent kinase 4 nuclear translocation.

177 ration or overexpression of the cyclin D1 or cyclin-dependent kinase 4 oncoproteins.

178 as two indolocarbazole-derived inhibitors of cyclin-dependent kinase 4 or 6 induced deletion of the f

179 ease unless it is responding to increases in cyclin-dependent kinase-4 or other cell cycle regulators

180 ation of cyclin D1 expression, inhibition of cyclin-dependent kinases 4 or 2 activity by small molecu

181 ves binding to and inactivating the cyclin D-cyclin-dependent kinase 4 (or 6) complex, and thus rende

182 p27(Kip1) loss with epithelial cell-specific cyclin-dependent kinase 4 overexpression identifies the

183 We examined the expression of the cyclin-dependent kinase 4, p34PSK-J3/cdk4 protein, in sm

184 oliferating cell nuclear antigen, cyclin D1, cyclin-dependent kinase 4, p53, cytokeratin 14, epiderma

185 on of several important molecules, including cyclin-dependent kinase 4, p53, mouse double minute 2 (M

186 ction of HSP72 and depletion of ERBB2, CRAF, cyclin-dependent kinase 4, phospho-AKT/total AKT, and hy

187 d the decrease in cyclin D1, D2, and D3, and cyclin-dependent kinase 4 protein.

188 ed a decrease in cyclins D1, D2, and D3, and cyclin-dependent kinase 4 proteins, and a concomitant de

189 21 and decreased expression of cyclin D1 and cyclin-dependent kinase 4 proteins.

190 human malignancies, and p16(INK4a)-cyclin D1-cyclin-dependent kinase 4-RB pathway aberrations are pre

191 ependent kinase 2 mutants bearing equivalent cyclin-dependent kinase 4 residues, namely F82H, L83V, H

192 Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine

193 cyclin-dependent kinase 2-specific, but not cyclin-dependent kinase 4-specific, sites in a p21-depen

194 er hand, the late induction of cyclin D1 and cyclin-dependent kinase 4 was indicative of possible cel