ライフサイエンスコーパス: KIP2

1 east two other genes in this locus (IPL, p57(KIP2)).

2 of the cyclin-dependent kinase inhibitor p57(Kip2).

3 e CKIs p21(Cip1), p14(ARF), p27(Kip1) or p57(Kip2).

4 family members, such as p27 (KIP1) and p57 (KIP2).

5 ease levels of p21(CIP1), p27(KIP1), and p57(KIP2).

6 bitors includes p21(Cip1), p27(Kip1) and p57(Kip2).

7 ase of apoptotic cells in the absence of p57(Kip2).

8 t kinase inhibitors (CKI), p27(Kip1) and p57(Kip2).

9 teins and resulted in phosphorylation of p57(Kip2).

10 dynein to the microtubule plus end requires Kip2.

11 n, and a dynamic plus end pool maintained by Kip2.

12 dependent upon the microtubule motor protein Kip2.

13 ubule polymerases, such as the yeast protein Kip2.

14 , encoding negative cell-cycle regulator p57-Kip2.

15 Bik1 forms a complex with the kinesin Kip2.

16 By Western blot analysis, expression of p57(KIP2), a known marker of terminally differentiated fiber

17 ified with loss-of-function mutations in p57(KIP2), a maternally expressed gene encoding a G(1) cycli

18 ciated with reduced expression of Cdkn1c/p57/Kip2, a cell cycle inhibitor, and increased expression o

19 She1 has no effect on the motility of either Kip2, a kinesin that utilizes the same microtubule track

20 d Clip170-are sufficient to couple dynein to Kip2, a plus-end-directed kinesin.

21 e CDK inhibitors p21(CIP), p27(KIP), and p57(KIP2) all promote the association of cdk4 with the D-typ

22 expression of the maternally inherited p57 (KIP2) allele lie at a distance from the gene.

23 Both KIP2 alleles are expressed but there is a bias with the

24 ethylation of the imprinted H19 allele, both KIP2 alleles are hypomethylated and WTs with biallelic H

25 centromeric domain including KVLQT1 and p57(KIP2), alterations in which are more common in BWS, and

26 cyclin-dependent kinase inhibitor (CKI) p57(KIP2), an important regulator of G1 phase, using deletio

27 evated MXD1, MAXI2, DUSP5, p27/KIP1, and p57/KIP2 and decreased Cyclin D and CDK genes can be expecte

28 rexpressing two CDK-specific inhibitors, p57/KIP2 and p21/CIP1.

29 gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a predicted multi-membrane-spanni

30 but that the allelic bias at Ipl, Impt1, p57 Kip2 and, to a lesser extent, Kvlqt1, persisted.

31 splay ectopic and elevated expression of p57(kip2) and a dramatic reduction in proliferative activity

32 vel of cyclin-dependent kinase inhibitor p57(KIP2) and an increase in the level of cyclin D3 as compa

33 activation of p21(cip1), p27(kip1), and p57(kip2) and decreased myocyte proliferation.

34 BWS that both harbors a null mutation in p57(Kip2) and displays loss of Igf2 imprinting.

35 having the broadest expression, and both p57(Kip2) and p21(Cip1) showing transient expression in rest

36 onclusion, our observations suggest that p57(KIP2) and p27(KIP1) control neuronal output for distinct

37 ssociated with its ability to upregulate p57(Kip2) and p27(Kip1) while downregulating Pax6 expression

38 a in mice de-repressed the expression of p57(Kip2) and prevented glomerular injury in RPGN.

39 t that cyclin-dependent kinase inhibitor p57(Kip2) and vascular endothelial growth factor mRNAs are s

40 vlqt1) and Cd81 (Tapa-1) between Cdkn1c (p57(Kip2)) and Mash2.

41 egulators, such as p21(Cip1), p27(Kip1), p57(Kip2), and cyclin E.

42 ng p107, p130, p21(CIP1), p27(KIP1), and p57(KIP2), and is associated with cyclin.CDK complexes in vi

43 pend on H19 for their imprinting, Mash2, p57(Kip2), and Kvlqt1 are unaffected by a deletion of the H1

44 inhibitors (CKIs) p21(Cip1), p27(Kip1), p57(Kip2), and p130 for degradation.

45 ed CKIs in vivo, particularly p27(Kip1), p57(Kip2), and p130.

46 checkpoint regulators such as p27(Kip1), p57(Kip2), and the aurora kinases through both an Akt-mediat

47 r cell differentiation, including Prox1, p57(KIP2), aquaporin 0 and beta-crystallins.

48 e studies demonstrate that p27(KIP1) and p57(KIP2) are critical terminal effectors of signal transduc

49 of development, when both p27(Kip1) and p57(Kip2) are expressed in retinal progenitor cells, they we

50 expressed genes, H19, Mash2, Kvlqt1, and p57(Kip2), as well as two paternally expressed genes, Igf2 a

51 w that the CLIP-170 ortholog Bik1 stabilizes Kip2 at microtubule ends where the motor domain of Kip2

52 the methylation levels of p73, p15, and p57(KIP2) at the time of initial remission in 199 patients w

53 of Kip2 dynamics reveal that disrupting the Kip2-Bik1 interaction aborts Kip2 dwelling at microtubul

54 ession of the Cdkn1c gene (also known as p57(Kip2)) but does not interfere with maintenance of imprin

55 Dynein is transported to the plus end by Kip2, but is not a passive passenger, resisting its own

56 considerably reduced after inhibition of p57(KIP2) by small interfering RNA, IEX-1 overexpression, an

57 r mechanism underlying the regulation of p57(Kip2) by the Lhx genes, we combined chromatin immunoprec

58 Likewise, induced expression of KIP2 caused spindles to mislocalize in cells deficient f

59 ) is a member of the p21(Cip1)/p27(Kip1)/p57(Kip2) CDK inhibitor family and inhibits CDK2-cyclin E in

60 tain several imprinted genes, including p57 (KIP2) ( CDKN1C ) and IGF2.

61 ggests that a key imprinting element for p57(Kip2) (Cdkn1c) also lies at a distance.

62 Only two of these genes, p57(KIP2) (CDKN1C) and IGF2, are likely to be functionally i

63 idence for allele-specific expression of p57(Kip2) (Cdkn1c) from our bacterial artificial chromosome

64 key elements for expression of the mouse p57(Kip2) (Cdkn1c) gene also lie at a distance.

65 l of Prox1, Jag1, p27(Kip1) (Cdkn1b) and p57(Kip2) (Cdkn1c) gene expression.

66 ruption of appropriate expression of the p57(KIP2) (CDKN1C) gene through mutations that occur at a su

67 criptional profiling, we discovered that p57(Kip2) (Cdkn1c), encoding a cell cycle inhibitor, was up-

68 e, the cyclin-dependent kinase inhibitor p57(Kip2) (Cdkn1c).

69 criptional repressors, we discover that p57 (Kip2, CDKN1C) transcription is significantly upregulated

70 ssion at three imprinted loci, H19, IGF2 and KIP2, clustered on chromosome 11p15.5.

71 rsistent KIP2 mRNA expression and absence of KIP2 coding mutations showed full inactivation of H19.

72 Fluorescently labeled Bik1 and Kip2 comigrate along individual microtubules.

73 The observation that deletion of KIP2 could also suppress the inviability of dyn1Delta ka

74 arly to the mouse homologue, inactivation of KIP2 could occur via genomic imprinting.

75 We have found that the p57(Kip2) cyclin kinase inhibitor is upregulated during G(1)

76 We show that p57(Kip2) (cyclin-dependent kinase inhibitor protein 2) and

77 Levels of p21(Cip1/Waf1), p57(Kip2), cyclin A and cyclin E, all of which are also invo

78 Furthermore, p57(KIP2) deficiency markedly increased RGC and IPC division

79 pe and E cyclins was most evident in the p57(KIP2)-deficient lens wherein cyclin D overexpression ind

80 r the inappropriate proliferation in the p57(Kip2)-deficient retinae to preserve the correct proporti

81 ation following MEKi withdrawal drives a p57(KIP2)-dependent G1 cell cycle arrest and senescence or e

82 These findings reveal a central role for Kip2-dependent transport in the cell cycle control of mi

83 inase inhibitor Dacapo (Dap; ortholog of p57(KIP2)) determines whether NSCs enter G(0) or G(2) quiesc

84 At this stage, p57(Kip2 )did not regulate proliferation.

85 a muscle-specific regulatory element of p57(kip2) directly activated by MRFs in myoblasts but repres

86 hylation lack comparable hypermethylation of KIP2 DNA.

87 (p15(Ink4b), p16(Ink4a), p21(Cip1), and p57(Kip2)) do not induce cleavage of cyclin A; other cyclins

88 ion and imprinting of Mash2, Kvlqt1, and p57(Kip2) during development in embryonic and extraembryonic

89 disrupting the Kip2-Bik1 interaction aborts Kip2 dwelling at microtubule ends and abrogates its micr

90 -cell imaging and mathematical estimation of Kip2 dynamics reveal that disrupting the Kip2-Bik1 inter

91 ities are integrated at the level of the p57(kip2) enhancer to regulate the decision between progenit

92 Retinae from mice lacking p57(Kip2) exhibited inappropriate S-phase entry and apoptoti

93 (m1) LSKs leads to normalization of both p57-Kip2 expression and growth control.

94 ases with H19 inactivation also have reduced KIP2 expression and most cases with persistent H19 expre

95 ession in RD RMS cells but does not activate KIP2 expression.

96 ing is required to repress p21(cip1) and p57(kip2) expression in muscle progenitor cells.

97 which Lhx6 and Lhx8 negatively regulate p57(Kip2) expression in the prospective palate area to allow

98 p57(KIP2) expression is required for loss of BRAF(V600E) amp

99 ce myelopoiesis by transiently enhancing p57(KIP2) expression levels.

100 ition to cancer, suggesting that loss of p57(KIP2) expression may play a role in the condition.

101 etes setting by regulating cyclin D3 and p57(KIP2) expression through the S1P signaling pathway.

102 Moreover, p27(KIP1) and p57(KIP2) expression were reduced, suggesting downregulation

103 is and cyclin E, increased p27(KIP1) and p57(KIP2) expression, and prevented IGF-1-induced cyclin E m

104 element important for the regulation of p57(KIP2) expression.

105 in ES cells and generated mice devoid of p57(Kip2) expression.

106 h also exhibited increased p27(Kip1) and p57(Kip2) expression.

107 ion by maintaining Bmp10 and suppressing p57(kip2) expression.

108 nd E by 6 h, and decreased p27(KIP1) and p57(KIP2) expression.

109 ow that the Cdk inhibitors p27(KIP1) and p57(KIP2) function redundantly to control cell cycle exit an

110 eration over that induced by the loss of p57(KIP2) function.

111 on levels and DNA methylation of the 11p15.5 KIP2 gene in normal human tissues, WTs and embryonal rha

112 mutation in the cdk-inhibitor domain of the KIP2 gene in one of five cases of BWS.

113 Deletions of the KIP2 gene or point mutations at the region encoding the

114 The KIP2 gene was characterized by Southern blot, comparativ

115 f p57(Kip2) in vivo, we have ablated the p57(Kip2) gene by homologous recombination in ES cells and g

116 b human genomic fragment containing the p57 (KIP2) gene in transgenic mice.

117 Most significantly, the deletion of KIP2 greatly suppressed the spindle localization defect

118 These findings indicate that p57(Kip2) has an important role during mouse development tha

119 p57(Kip2) has been considered a candidate tumor suppressor g

120 p57(Kip2) has been linked to Beckwith-Wiedemann syndrome and

121 Consequently, we propose that p57(Kip2) has two roles during retinal development, acting f

122 Mice lacking the imprinted Cdk inhibitor p57(KIP2) have altered cell proliferation and differentiatio

123 Mutations in human p57(Kip2) have been implicated in Beckwith-Wiedemann syndrom

124 170 and EB1, act as processivity factors for Kip2, helping it overcome dynein's intrinsic minus-end-d

125 t study to search for potential mutations of KIP2 in a cohort of 126 tumors composed of 75 soft tissu

126 (9.5%) patients, p15 in 33 (17.4%), and p57(KIP2) in 7 (3.7%); 140 (74%) patients had methylation of

127 itor cell cycle withdrawal that involves p57(Kip2) in a central role opposing latent Cyclin D1 and ot

128 i, where it associates with cyclin D and p57(Kip2) in active enzyme complexes.

129 We observed dramatic underexpression of p57(KIP2) in BiCHM, identical to that seen in complete HM of

130 Retroviral mediated overexpression of p57(Kip2) in embryonic retinal progenitor cells led to prema

131 In addition, overexpression of p57(Kip2) in LNCaP cells inhibited tumor formation in nude m

132 The specific functions of p57(Kip2) in lymphocytes have not yet been fully elucidated.

133 nhibitors p21(Waf1/Cip1), p27(Kip1), and p57(Kip2) in monkey kidney cells (CV-1).

134 ostate cancer, and the overexpression of p57(Kip2) in prostate cancer cells significantly suppressed

135 wever, little is known about the role of p57(Kip2) in tumorigenesis and cancer progression.

136 To investigate the role of p57(Kip2) in vivo, we have ablated the p57(Kip2) gene by hom

137 h acts by inducing expression of cdkn1c (p57(Kip2)) in slow muscle precursor cells, but neither Hh no

138 Consequently, loss of p57(KIP2) increased primarily layer 5-6 neuron production, w

139 the cell cycle inhibitors p27(kip1) and p57(kip2), increased apoptosis and aberrant or reduced expre

140 he deletion causes BWS with silencing of p57(KIP2), indicating deletion of an element important for t

141 ivation of cdk6, the ultimate outcome of p57(Kip2) induction was a decrease in DNA synthesis and cell

142 rced cyclin expression and/or of loss of p57(KIP2) inhibitor function in a cellular compartment that

143 cyclins D and E and up-regulation of the p57(KIP2) inhibitor in the postmitotic lens fiber cell compa

144 These data suggest that KIP2 is a BWS gene but that it is not uniquely equivalen

145 re, we report that the budding yeast kinesin Kip2 is a microtubule polymerase and catastrophe inhibit

146 controlling aMT regulating factors, of which Kip2 is a prime candidate, provide a framework to unders

147 The CDK inhibitor p57(Kip2) is a major target of miR-92a that constitutively s

148 p57(Kip2) is a paternally imprinted gene that encodes a pote

149 ted very differently by DNA methylation; p57(Kip2) is activated, Kvlqt1 is silenced, and Mash2 is una

150 ore, these results strongly suggest that p57(Kip2) is an important gene in prostate cancer tumorigene

151 The cyclin-dependent kinase inhibitor p57(kip2) is encoded by an imprinted gene Cdkn1c, with the p

152 The results indicate that p57(Kip2) is involved in the regulation of several aspects o

153 ic nuclei were found in the region where p57(Kip2) is normally expressed.

154 p57(Kip2) is primarily expressed in terminally differentiate

155 Here, we show that the expression of p57(Kip2) is significantly decreased in human prostate cance

156 p57(Kip2) is the first gene to be implicated as a regulator

157 ng the cyclin-dependent kinase inhibitor p57(Kip2) is the opposite of the PTHrP-null phenotype, we hy

158 To probe further the function of p57(Kip2), Jurkat cells stably transfected with a plasmid en

159 Furthermore, the prostates of p57(Kip2) knockout mice developed prostatic intraepithelial

160 ntains the imprinted genes TSSC3, TSSC5, p57(KIP2), KVLQT1, ASCL2, IGF2 and H19.

161 Included in the map are the CARS, NAP2, p57/KIP2, KVLQT1, ASCL2, TH, INS, IGF2, H19, and L23MRP gene

162 pha, glucose transporter-like protein 1, p57(Kip2), La, BiP, and triose phosphate isomerase transcrip

163 ubules by targeting Bik1 to the plus end and Kip2 levels are controlled during the cell cycle.

164 xpress similar levels of p57(Kip2), that p57(Kip2) levels increase over time in proliferating OPCs, a

165 ver time in proliferating OPCs, and that p57(Kip2) levels regulate how many times an OPC can divide b

166 Most notably, increased p57(Kip2) levels resulted in marked inhibition of both cycli

167 strate a role for the p21(CIP)/p27(Kip1)/p57(Kip2)-like cyclin-dependent kinase inhibitor (cki) dacap

168 ere, we identify the p21(Cip1)/p27(Kip1)/p57(Kip2)-like cyclin-dependent kinase inhibitor (CKI) Dacap

169 demonstrate that the p21(cip1)/p27(kip1)/p57(kip2)-like cyclin-dependent kinase inhibitor (CKI), Daca

170 The p57(Kip2) locus has been implicated in the Beckwith-Wiedeman

171 in expression of marker genes including p57(KIP2), Maf and Prox1.

172 king p107 and p130, thus suggesting that p57(Kip2) might be an upstream regulator of these Rb-related

173 s, and several of the tumors with persistent KIP2 mRNA expression and absence of KIP2 coding mutation

174 th LOH show moderate to marked reductions in KIP2 mRNA relative to control tissues and residual mRNA

175 rimary WTs enriched for cases that expressed KIP2 mRNA, including cases with and without 11p15.5 loss

176 ersistent H19 expression have high levels of KIP2 mRNA.

177 Most p57(Kip2) mutant mice have short limbs, a defect attributabl

178 Developmental defects of p57(Kip2) mutant mice include cleft palate and gastrointesti

179 ved neoplastic development even in those p57(Kip2) mutant mice that have survived for >5 months of ag

180 The absence of KIP2 mutations might indicate that these tumors arise du

181 Prox1 and p57(KIP2), normally upregulated at the onset of fiber differ

182 Most p57(Kip2) null mice die after birth and display severe devel

183 Releasing Kip2 of its control by SPBs equalizes its distribution,

184 how that de-repression of p57 (also known as KIP2 or CDKN1C) upon combined BET and HDAC inhibition is

185 p15 and including infrequent mutation of p57(KIP2) or loss of imprinting of either of two imprinted g

186 (p15(INK4b), p21(CIP1/WAF1), p27(KIP1), p57(KIP2)) or to repress c-myc and Bcl-2 transcription.

187 ne domains on 11p15: LIT1, which is near p57(KIP2), or H19/IGF2.

188 ibitors, including p21(CIP1), p27(KIP1), p57(KIP2), p16(INK4a), and p18(INK4c), could block phosphory

189 Analysis of p57(Kip2);p27(Kip1) double mutants, where p21 expression is

190 Here, we identified p57(Kip2) (p57) as a molecular switch for the reserve stem c

191 n prostate cancer tumorigenesis, and the p57(Kip2) pathway may be a potential target for prostate can

192 es including H19 (H19 fetal liver mRNA), p57(Kip2), Peg3/Pw1 (paternally expressed gene 3), and Zac1

193 and Bfa1, and phosphorylation of cytoplasmic Kip2 prevents random lattice binding.

194 t microtubule ends where the motor domain of Kip2 promotes microtubule polymerization.

195 , it was shown in vitro that addition of p57(Kip2) protein to a mixture of cyclin D2 and cdk6 enhance

196 Kip2 recruitment at the SPB depends on Bub2 and Bfa1, an

197 w that two Cdk inhibitors, p21(CIP1) and p57(KIP2), redundantly control differentiation of skeletal m

198 To investigate the p57 (KIP2) region, we similarly tested the imprinting and fun

199 amics analyses in mutants indicated that p57(KIP2) regulates cell cycle length in both RGCs and IPCs.

200 le of PR-domain-containing ME in linking p57-kip2 regulation to long-term HSC function.

201 Human KIP2 resides in 11p15.5, a chromosomal region that is a

202 tion by directly targeting p27(Kip1) and p57(Kip2), respectively.

203 Induction of p57(Kip2) resulted in increased association of cdk6 with cyc

204 , p21(CIP1), p15(INK4b), p16(INK4a), and p57(KIP2) reveals altered expression in immortalized, non-tu

205 Levels of p16(INK4a) and p57(KIP2) rise in HUCs during progressive passages, whereas

206 te stage of development, animals lacking p57(Kip2) showed an alteration in amacrine subpopulations.

207 Kip2 stabilizes microtubules by targeting Bik1 to the pl

208 Although the KipA kinesin (Kip2/Tea2 homologue) did not affect plus-end localizatio

209 clone of OPCs express similar levels of p57(Kip2), that p57(Kip2) levels increase over time in proli

210 hree distinct genes, p21, p27(Kip1), and p57(Kip2), that share a common N-terminal domain for binding

211 or myogenic growth arrest (p21(cip1) and p57(kip2)), the Notch pathway and myogenic regulatory factor

212 Here we evaluate the expression of p57(KIP2), the product of CDKN1C, an imprinted, maternally e

213 ralizing this patch abolished the ability of Kip2 to promote microtubule growth both in vivo and in v

214 cyclin E/CDK2 and antagonistically with p57(KIP2) to regulate the G1/S transition in a cell type hig

215 ably transfected with a plasmid encoding p57(Kip2) under control of an inducible (tetracycline) promo

216 ggest that loss of Cdkn1c imprinting and p57(KIP2) upregulation alters the cellular composition of th

217 Our studies suggest that Kip2 utilizes Bik1 as a cofactor to track microtubule ti

218 s indicated that LHX6 and LHX8 regulated p57(Kip2) via both direct and indirect mechanisms, with the

219 Postnatally, p57(Kip2) was found to be expressed in a novel subpopulation

220 In contrast, no somatic coding mutations in KIP2 were found in a set of 12 primary WTs enriched for

221 approaches, we found that p27(Kip1) and p57(Kip2) were 2 target genes that were involved in miR-221-

222 the cell cycle inhibitors p27(Kip1) and p57(Kip2) were selectively overexpressed in duodenal and ile

223 In this study, it is shown that p57(Kip2), which is a member of the Cip/Kip family of cyclin

224 the cyclin-dependent kinase inhibitor called KIP2, which inhibits several G1 cyclin-cyclin-dependent

225 e old SPB recruits the kinesin motor protein Kip2, which then translocates to the plus-end of the ema