ライフサイエンスコーパス: p16INK4A

1 e manner with those of the senescence marker p16INK4A.

2 e activity and is inhibited by cyclin D1 and p16INK4a.

3 at FOXP1 directly represses transcription of p16INK4A.

4 n of cell cycle inhibitory proteins, such as p16INK4a.

5 alyzed them for mutations in p53 and loss of p16ink4a.

6 not exclude patients with known mutations in p16INK4A.

7 ion of the cyclin-dependent kinase inhibitor p16INK4A.

8 melanomas experience high-frequency loss of p16INK4a.

9 families carrying CDKN2A mutations affecting p16INK4A.

10 lines are resistant to growth inhibition by p16INK4a.

11 , they failed to arrest in G1 in response to p16INK4a.

12 The expression pattern is similar to that of p16INK4A.

13 or tumors that have wt-p53 but nonfunctional p16INK4a.

14 n, leading to nuclear accumulation of mutant p16ink4a.

15 ction in regulating expression of VEGF-A and p16INK4a.

16 sensitive tumor suppressor genes Rassf1a and p16INK4a.

17 l who is homozygous for the R24P mutation in p16INK4a.

18 and not or rarely at SDHB (4%), RARB2 (0%), p16INK4a (0%) and CDH13 (3%).

19 e frequencies at NORE1A (15%), p14ARF (15%), p16INK4a (10%), DAPK (11%) and CRBP1 (9%), but promoter

20 hout mutations affecting p16INK4A (wild-type p16INK4A); 191 probands from melanoma-prone families wit

21 462) in all melanoma patients with wild-type p16INK4A, 2.6% (7 of 271) in those with MPM, and 2.9% (2

22 in 40% for RARbeta, 26% for TIMP-3, 25% for p16INK4a, 21% for MGMT, 19% for DAPK, 18% for ECAD, 8% f

23 ligase that targets p53 for degradation, and p16INK4a, a member of the Rb tumor suppressor pathway.

24 erepression of non-muscle-specific genes and p16INK4a, a senescence driver encoded in the Cdkn2a locu

25 ion of the cyclin-dependent kinase inhibitor p16INK4a abrogated the CSC properties of iCSCL-10A cells

26 determine the physiological significance of p16INK4a accumulation on islet function, we assessed the

27 e influence of adenovirus-mediated wild-type p16INK4a (Ad/p16) expression on the radiation sensitivit

28 These data establish that p16Ink4a, along with p19Arf, functions as a tumour suppr

29 Using p16ink4a, an upstream activator of endogenous RB, or a c

30 reading frames in the INK4A/ARF gene encode p16INK4a and a distinct tumour-suppressor protein, p19AR

31 The age-associated increase in expression of p16INK4a and Arf is attenuated in the kidney, ovary, and

32 We show that expression of p16INK4a and Arf markedly increases in almost all rodent

33 locus encodes 2 tumor suppressor molecules, p16INK4a and Arf, which are principal mediators of cellu

34 e of CtBP1 in the transcriptional control of p16INK4a and Brca1, with CtBP1 overexpression potentiall

35 y the expression of the cell cycle inhibitor p16INK4a and cell death by hairpin 1 and 2.

36 However, it is not understood why p16INK4a and cyclin D:cdk4/6 mutations are disproportion

37 HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50.

38 l analysis, immunohistochemical staining for p16INK4a and Ki67, HPV-typing, and viral load determinat

39 to trigger senescence, which is mediated by p16INK4A and lacks a canonical senescence-associated sec

40 This has led to the suggestion that it is p16INK4a and not p14ARF that plays the critical role in

41 notype accompanied by elevated expression of p16INK4A and other markers for senescence.

42 rther promoted tumor suppressor functions of p16Ink4a and p14/p19Arf directed against CDK4/6-mediated

43 kinase inhibitor 2A (CDKN2A) locus (encoding P16INK4A and P14ARF) in a large number of tumors within

44 CDKN2A locus encodes two distinct proteins, p16INK4a and p14ARF, both of which are implicated in rep

45 noma susceptibility gene is CDKN2A, encoding p16INK4A and p14ARF.

46 ted to inactivate the coding regions of both p16INK4a and p14ARF.

47 ocus encodes two distinct tumor suppressors, p16INK4a and p14ARF.

48 Ink4a, p19Arf and Trp53 (triple mutant mice; p16Ink4a and p19Arf are alternative reading frames of th

49 enetic studies provide definitive proof that p16INK4a and p19ARF cooperate to suppress the developmen

50 eral lines of evidence support the view that p16INK4a and p19ARF exert the tumor-suppressor activitie

51 iption of the negative cell cycle regulators p16Ink4a and p19Arf from the Cdkn2a locus.

52 Expression of p16Ink4a and p19Arf in normal HSCs resulted in prolifera

53 hort hairpin RNA-mediated acute knockdown of p16Ink4a and p19Arf p16(Ink4a) and p19(Arf) indicates th

54 ned that noncleaved TFIIA accumulates at the p16Ink4a and p19Arf promoters to drive transcription of

55 neous B16 melanoma cell lines, expression of p16Ink4a and p19Arf tumor suppressor proteins was lost a

56 and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of

57 s, including Mtap, the 2 isoforms of Cdkn2a, p16Ink4a and p19Arf, and Cdkn2b, in atherosclerosis usin

58 erences in the sensitivity of progenitors to p16Ink4a and p19Arf.

59 Furthermore, we found that hSNF5 bound the p16INK4a and p21CIP/WAF1 promoters, suggesting that it d

60 nalogous to normal cellular senescence, both p16INK4a and p21CIP/WAF1 were up-regulated following hSN

61 nescence, we examined the activation of both p16INK4a and p21CIP/WAF1.

62 h levels of the G(1)-specific CDK inhibitors p16Ink4a and p21Cip1 and senesced prematurely; this defe

63 ion of either of the two key CDK inhibitors, p16Ink4a and p21WAF1, but is consistent with a different

64 ed differences in the relative expression of p16INK4a and p21WAF1/Cip1 and in the kinetics of Rb hype

65 studies revealed an age-related increase in p16INK4a and p21WAF1/Cip1 protein expression in cultured

66 in negative regulation of the cell cycle by p16INK4a and p21WAF1/Cip1.

67 riggers autophagy and that the RB activators p16INK4a and p27/kip1 induce autophagy in an RB-dependen

68 Cdk inhibitors such as p16INK4a and p27Kip1 inhibit pRb phosphorylation by the

69 inoma) cells were resistant to expression of p16ink4a and PSM-RB.

70 ma diagnosis and without mutations affecting p16INK4A, and 69 probands from different families carryi

71 hSNF5 induces G1 cell cycle arrest, elevated p16INK4a, and activated replicative senescence markers,

72 of the senescent associated proteins p53 and p16INK4a, and apoptosis of CPCs, impairing the growth re

73 preferred serine 612, which was inhibited by p16INK4a, and fascaplysin.

74 n of silencing of the tumour suppressor gene p16INK4a, and growth suppression.

75 ns were found: deletion of ETV6, deletion of p16INK4A, and hyperdiploidy, as well as a number of nove

76 RasV12 failed to induce p53, p19ARF, p16INK4a, and p15INK4b expression in KSR1-/- MEFs and in

77 uding acidic beta-gal staining, induction of p16INK4a, and p15INK4b expression.

78 arrest and senescence, such as p27Kip1, p53, p16INK4a, and p19ARF, were detected in myocytes of young

79 associated beta-galactosidase (SA-beta-gal), p16Ink4a, and p53 in lamin A/C-deficient muscles and C2C

80 encodes two cell cycle-regulatory proteins, p16INK4a andp14ARF, which share an exon using different

81 Abnormally high levels of p16INK4a are commonly observed in human papillomavirus (

82 cence presumably underlies the importance of p16INK4a as a tumour suppressor but the mechanisms regul

83 Additionally, p16ink4a attenuated the levels of the assembly factors C

84 ons in the CDKN2A locus that include ARF and P16INK4A, both of which encode tumor suppressor proteins

85 cell lines, all of which lacked constitutive p16INK4a but each of which varied in p53 status: A549 (-

86 inogen-induced melanoma cell lines expressed p16Ink4a but had inactivating mutations in either p19Arf

87 Restoration of p16INK4a but not p19ARF suppressed PDGFRalpha-promoted g

88 e pancreas, and islet-specific expression of p16INK4a, but not other cyclin-dependent kinase inhibito

89 The induction of p16INK4a by Ets2, which is abundant in young human diplo

90 p16INK4a expression, as siRNA suppression of p16INK4a bypasses tetraploid arrest, permitting primary

91 emonstrates that alterations in both p53 and p16ink4a can contribute to RDEB associated SCC.

92 The cyclin-dependent kinase inhibitor p16INK4a can induce senescence of human cells, and its l

93 the cyclin-dependent kinase (CDK) inhibitors p16INK4A (CDKN2A) and p21CIP1 (CDKN1A), increased secret

94 However, HPrECs expressing c-Myc lack a Rb/p16INK4a checkpoint and can be transformed without the n

95 sociated with low expression of p15ink4b and p16ink4a, constitutive Rb phosphorylation and high level

96 Here we show that p16INK4a constrains islet proliferation and regeneration

97 ture, protein levels of the tumor suppressor p16INK4a continue to increase, resulting in growth arres

98 Mutations in the p16INK4A cyclin-dependent kinase inhibitor (CDI) gene at

99 The p16INK4a cyclin-dependent kinase inhibitor is implicated

100 is enhanced by another major POAG risk gene, p16INK4a (cyclin-dependent kinase inhibitor 2A, isoform

101 Expression of p16ink4a, cyclin D1, Cdk4, and Rb in relation to that of

102 ved mutations has led to the suggestion that p16INK4a, cyclin D1, cdk4, and the retinoblastoma protei

103 The p16ink4a-cyclin D1/cyclin-dependent kinase 4 (Cdk4)-reti

104 Deregulation of the p16INK4a-cyclin D:cyclin-dependent kinases (cdk) 4/6-ret

105 on islet function, we assessed the impact of p16INK4a deficiency and overexpression with increasing a

106 p16INK4a deficiency did not detectably affect progenitor

107 larly, islet proliferation was unaffected by p16INK4a deficiency in young mice, but was relatively in

108 p16Ink4a deficiency partially reverses the self-renewal

109 Furthermore, p16Ink4a deficiency was associated with an increased inc

110 Compound deficiency of Cdkn2a, especially p16Ink4a deficiency, markedly reduced the craniofacial a

111 vertheless, Milan HDFs behave as if they are p16INK4a deficient, in terms of sensitivity to spontaneo

112 Ageing p16INK4a-deficient mice showed a significantly smaller d

113 ients), TP53 (mutated in 11 of 41 patients), p16INK4A (deleted in 15 of 33 patients), or phosphatase

114 se inhibitor 2A (CDKN2A, encoding p14ARF and p16Ink4a) deletions in pediatric infiltrative astrocytom

115 ed with advancing age; however, mice lacking p16INK4a demonstrated enhanced islet proliferation and s

116 derived superoxide as a driver of protumoral p16INK4a-dependent senescence in BM stromal cells.

117 Specifically, p16ink4a disrupts prereplication complex assembly by inh

118 We found that expression of p16INK4a dramatically affects radiation sensitivity of H

119 T cells deficient in p16Ink4a exhibited enhanced mitogenic responsiveness, co

120 The p16INK4a-expressing senescent stromal cells then feed ba

121 n the p16INK4a-RB pathway: (1) repression of p16INK4a expression and (2) blocking the downstream medi

122 conditions have been shown to modulate both p16INK4a expression and replicative capacity of human ke

123 nhanced proliferation but eventually induced p16INK4A expression and senescence.

124 NK4a methylation was correlated with loss of p16INK4a expression by immunohistochemistry.

125 response of neural progenitors to increased p16INK4a expression during ageing.

126 K signalling decline, the marked increase in p16INK4a expression is consistent with the reciprocal re

127 Importantly, endogenous p16INK4a expression is not detected in six PEL derived c

128 sults demonstrate that a sustained period of p16INK4a expression is sufficient in this setting to imp

129 ort the view that an age-induced increase of p16INK4a expression limits the regenerative capacity of

130 CC patient samples revealed that high levels p16INK4a expression significantly correlated with decrea

131 Bmi-1 to promote self-renewal and to repress p16Ink4a expression suggests that a common mechanism reg

132 By contrast, p16ink4a expression was reduced or absent.

133 In this tissue compartment, p16ink4a expression was strongly associated with disease

134 Higher levels of p16INK4a expression were present in cells that also disp

135 s inhibited, both keratinocyte migration and p16INK4a expression were reduced.

136 dyplasia cultures (that retain RAR-beta and p16INK4A expression) does not extend their lifespan, eve

137 -1 protein expression, increased Rassf1a and p16INK4a expression, and reduced cell proliferation.

138 ed activated by hSNF5 in the absence of high p16INK4a expression, apparently causing the growth arres

139 Tetraploid arrest is dependent on p16INK4a expression, as siRNA suppression of p16INK4a by

140 n and that this state becomes independent of p16INK4a expression, hypophosphorylation of pRB, or a st

141 /or IOP promotes POAG by directly increasing p16INK4a expression, leading to RGC senescence in adult

142 oss of retinoic acid receptor (RAR)-beta and p16INK4A expression, p53 mutations and activation of tel

143 posure to a high-fat diet did not accelerate p16INK4a expression, whereas arsenic modestly augmented,

144 X6 risk alleles (CC) leads to an increase in p16INK4a expression, with subsequent cellular senescence

145 ageing are thus caused partly by increasing p16INK4a expression.

146 actosidase (beta-gal) activity and increased p16INK4a expression.

147 ne expression, thereby reducing the level of p16INK4a expression.

148 ls is mediated in part through activation of p16ink4a expression.

149 steogenic sarcoma cell clones with inducible p16INK4a expression.

150 the BM stromal cell senescence is driven by p16INK4a expression.

151 ion of cyclin-dependent kinase inhibitor 2A (p16INK4A) expression.

152 Induction of p16INK4a for 1 day arrested most cells in G1 phase.

153 Combined, these data reveal that RB and p16ink4a function through distinct pathways to inhibit t

154 Ultraviolet light and deficiency of the p16ink4a gene are known factors that predispose one to t

155 ich is an important transcription factor for p16INK4a gene expression, thereby reducing the level of

156 , it has been unclear how LMP1 represses the p16INK4a gene expression.

157 in this pathway, homozygous deletion of the p16INK4A gene, is commonly observed in head and neck squ

158 to these carcinogens and inactivation of the p16INK4A gene.

159 r, no point mutations in p14ARF not altering p16INK4a have been described in primary tumors.

160 The odds ratio (OR) for p16INK4A homozygous deletion among alcohol consumers in

161 Hypothesizing that p16INK4A homozygous deletion is associated with tobacco

162 Notably, in the absence of p16INK4a, HSC repopulating defects and apoptosis were mi

163 from patients with RDEB for the presence of p16ink4a hypermethylation, and found two tumors that hav

164 arrested cells exhibited strong induction of p16ink4a, hypophosphorylated RB, and down-regulation of

165 associated beta-galactosidase (SA-beta-Gal), p16INK4A, IL-6, and IL-8.

166 Furthermore, high expression of p16ink4a in conjunction with Ki-67 was associated with i

167 ess, consistent with the established role of p16Ink4a in constraining cellular proliferation.

168 Particularly, the elevated expression of p16ink4a in DCIS was associated with loss of RB function

169 Loss of p16INK4A in Foxp1-deficient MSCs partially rescued the d

170 However, the functional role of p16INK4a in HNSCC remains unexplored.

171 se findings reveal an unexpected function of p16INK4a in homologous recombination-mediated DNA repair

172 S, and, surprisingly, elevated expression of p16ink4a in nonproliferative stroma was observed in a su

173 Our results implicate p16INK4a in regulation of homologous recombination-media

174 Here, we demonstrate a novel role for p16ink4a in replication control that is distinct from th

175 ominant-negative BRG-1, arrest by PSM-RB and p16ink4a in the absence of dominant-negative BRG-1 expre

176 We then evaluated the role of p19Arf and p16Ink4a in the loss of HSCs during serial transplantati

177 provide evidence that ectopic expression of p16INK4a in these cells causes an Rb dependent G1 cell c

178 creased expression of the senescence marker, p16Ink4a, in N-WASP-deficient epidermis.

179 ion coupled with microsatellite instability, p16Ink4a inactivation, and p53 mutation in the serrated

180 well as EZH2, extends throughout p14ARF and p16INK4a, indicating that polycomb repression of p15INK4

181 We infer that p16INK4a-induced arrest is not mediated exclusively by p

182 bers, we find that pRB is insufficient for a p16INK4a-induced arrest.

183 4/5 are essential downstream mediators for a p16INK4a-induced cell cycle arrest, these results indica

184 inocyte cell strains, we verified a delay in p16INK4a induction and an extended lifespan of human ker

185 man keratinocytes; however, the mechanism of p16INK4a induction under these conditions is unknown.

186 Moreover, if p16INK4a induction was interrupted at this point and the

187 and human cells harboring the melanoma-prone p16Ink4a-insensitive CDK4R24C mutation, we show here tha

188 ted by inhibition of CDK4/6 by PD-0332991 or p16ink4a irrespective of RB status.

189 Deregulation of p16INK4A is a critical event in melanoma susceptibility

190 The tumor suppressor p16INK4a is a potent mediator of cell cycle arrest in tr

191 p16INK4a is an effector of senescence and a potent inhib

192 hibit a migratory phenotype and suggest that p16INK4a is selectively induced under these conditions b

193 , the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing t

194 ilation, tissue injury, and minimal level of p16INK4a labeling.

195 If the induction was then interrupted, p16INK4a levels returned to baseline and robust growth r

196 of the heterochromatic domains of the p14ARF/p16INK4a locus in T24 bladder cancer cells, reducing lev

197 r primary PEL samples and examination of the p16INK4a locus shows deletion in two out of six and hype

198 ariants, including those associated with the p16INK4A locus, which are associated with the presence o

199 Taken together these results suggest that p16INK4a loss may be a cellular change frequently associ

200 Inhibition of p16INK4a may ameliorate the physiological impact of agei

201 ient muscles and C2C12 muscle cells, and the p16Ink4a may induce senescence-associated secretory phen

202 d UV light potently augmented, activation of p16INK4a-mediated senescence.

203 notypic end point, we further show that RAS+ p16INK4a-/- melanomas sustain somatic inactivation of p1

204 alysed for RASSF1A promoter methylation, and p16INK4a methylation results were also available for the

205 ectal cancer and occurs independently of the p16INK4a methylation status and only marginally in relat

206 Moreover, p16INK4a methylation was correlated with loss of p16INK4

207 hort of Spanish patients with melanoma or in p16INK4A mutation carriers.

208 % (2 of 69) in the probands of families with p16INK4A mutations.

209 noma were available for screening of CDKN2A (p16INK4a) mutations.

210 tion of 1 biopsy, all low-grade lesions were p16INK4a-negative, whereas 25 of 31 (81%) AGWs with high

211 Compared with wild-type MEFs, p16Ink4a-null MEFs exhibited an increased rate of immort

212 bryo fibroblasts (MEFs) deficient in p19Arf, p16Ink4a-null MEFs possessed normal growth characteristi

213 e inhibitor of metalloproteinase 3 (TIMP-3), p16INK4a, O6-methylguanine-DNA-methyltransferase (MGMT),

214 This influence of p16ink4a on the prereplication complex was dependent on

215 tional RB since ectopic expression of either p16ink4a or a constitutively active form of RB (PSM-RB)

216 melanomas to examine the impact of germline p16INK4a or p19ARF nullizygosity on melanoma formation.

217 We hypothesized that expression of p16Ink4a or p19Arf or both may play a role in the loss o

218 ouse models demonstrate that inactivation of p16Ink4a or Rb (retinoblastoma) does not accelerate tumo

219 Osteosarcomas engineered to be deficient in p16INK4a or Rb exhibited impaired senescence and failed

220 ase was prevented by G1 blockade mediated by p16Ink4a or the CDK inhibitor roscovitine, whereas down-

221 e of the adenomatous polyposis coli, p14ARF, p16INK4a, or death associated protein-kinase tumor suppr

222 cdk4, especially a variant which cannot bind p16INK4a, overcame cell cycle inhibition resulting from

223 p16INK4a overexpression impairs the recruitment of RAD51

224 We and others found that p16INK4a overexpression is associated with improved ther

225 lockade of endogenous RB phosphorylation via p16ink4a overexpression.

226 xtended lifespan showed loss of RAR-beta and p16INK4A/p14ARF expression, but retained functional wild

227 MycN, in cooperation with down-regulation of p16INK4A/p14ARF expression, were necessary and sufficien

228 HD was detected only at the CDKN2A (p16INK4a/p14ARF) gene at 9p21 and was observed in 4 of 4

229 on of myoblasts, and a selection for loss of p16INK4A/p14ARF.

230 owed that while both specific CDK4 inhibitor p16INK4A (P16) and gankyrin bind to cyclin-dependent kin

231 with expression of the cell cycle inhibitor p16INK4A (p16) and of the basement membrane protein lami

232 ied SNPs near CDKN2A, the locus encoding for p16INK4a (p16), associated with elevated risk for cardio

233 homologue of the important tumor suppressor p16INK4A (p16).

234 were restricted, in part, by the function of p16INK4A-p19(ARF), which limited the temporal epoch for

235 three genes genetically downstream of Bmi1--p16Ink4a, p19Arf and Trp53 (triple mutant mice; p16Ink4a

236 cTECs and expressed relatively low levels of p16INK4a, p19ARF, and Serpine1, and high levels of Bmi1,

237 These results demonstrate that p16Ink4a/p19Arf and Trp53 have a central role in limitin

238 results indicate that genetic alterations in p16Ink4a/p19Arf, p53 and ras-MAPK pathways can cooperate

239 nd HMGB1, as well as increased expression of p16Ink4a, p21, and MMP-9.

240 genomic abnormalities, and induction of p53, p16Ink4a, p21Cip1, and senescence-associated beta-galact

241 Of those CKIs, p16INK4a, p21WAF1/Cip1, and p27Kip1 are expressed in cor

242 However, p16ink4a, p53 and p19ARF expression also increase during

243 at T-oligos act through ATM, p95/Nbs1, E2F1, p16INK4A, p53, and the p53 homologue p73 to modulate dow

244 l cells involves both inactivation of the Rb/p16INK4a pathway and telomere maintenance, and it has be

245 te hypertrophy and dilation, accumulation of p16INK4a positive primitive cells and myocytes, and no s

246 high-grade lesions or an anal carcinoma were p16INK4a-positive.

247 , H322 (-p16INK4a/ +pRb/mt-p53), and H1299 (-p16INK4a/ +pRb/deleted-p53).

248 tatus: A549 (-p16INK4a/ +pRb/wt-p53), H322 (-p16INK4a/ +pRb/mt-p53), and H1299 (-p16INK4a/ +pRb/delet

249 t each of which varied in p53 status: A549 (-p16INK4a/ +pRb/wt-p53), H322 (-p16INK4a/ +pRb/mt-p53), a

250 e results demonstrate that disruption of the p16INK4A/pRB checkpoint of epithelial cell immortalizati

251 f G1 arrest that requires the p19ARF/p53 and p16INK4a/pRB pathways and may suppress tumorigenesis in

252 s in the context of an adjacent unmethylated p16INK4a promoter in 16 of 31 (52%) of the carcinomas me

253 ctors based on their ability to activate the p16INK4a promoter through an ETS-binding site and their

254 orescent protein regulated by the endogenous p16Ink4a promoter) demonstrated the emergence of a p16-h

255 ar to human MPNST, and tumors showed reduced p16INK4a protein and reduced senescence markers, confirm

256 dministration of a membrane-transducible TAT-p16INK4a protein completely blocked hair follicle growth

257 The p16INK4a protein is a principal cyclin-dependent kinase

258 a-2' deoxycytidine leads to re-expression of p16INK4a protein.

259 The p16INK4a-RB pathway plays a critical role in preventing

260 (2) blocking the downstream mediator of the p16INK4a-RB pathway.

261 anding of how viral oncoproteins perturb the p16INK4a-RB pathway.

262 MP1 on nuclear export has two effects on the p16INK4a-RB pathway: (1) repression of p16INK4a expressi

263 ect transcriptional activator of p53-p21 and p16ink4a-Rb tumor suppression pathways.

264 ingly, we also found that, in the absence of p16INK4a, reexpression of hSNF5 also increased protein l

265 alysed, including the tumour suppressor gene p16INK4a, remained fully methylated and silenced.

266 codes a D type cyclin (kcyc) that can elicit p16INK4a resistant cdk activity and orf73 encodes the la

267 Using p16INK4a RNA interference, we showed its requirement for

268 DH1, CDH13, CRBP1, DAPK, MGMT, MT1G, NORE1A, p16INK4a, SDHB and RARB2 in primary RCC.

269 Importantly, selective elimination of p16INK4a(+) senescent BM stromal cells in vivo improved

270 mortalized cells that had lost expression of p16INK4A showed no such abnormalities.

271 At all time points, p16ink4a showed reduced nuclear staining in ZD esophagi

272 ibe the generation and characterization of a p16Ink4a-specific knockout mouse that retains normal p19

273 Mice lacking Mdm2 or p16INK4a stabilized mutant p53, and revealed an earlier

274 were HIV- showed no signs of dysplasia, and p16INK4a-staining was always negative.

275 ation-mediated DNA repair response and imply p16INK4a status as an independent marker to predict resp

276 reased and occurred only in cells expressing p16INK4a that had significant telomeric shortening.

277 t that the cyclin-dependent kinase inhibitor p16INK4a, the level of which was previously noted to inc

278 tion, and found two tumors that have loss of p16ink4a through hypermethylation.

279 Transgenic mice that overexpress p16INK4a to a degree seen with ageing demonstrated decre

280 Although the contribution of p16INK4a to human tumorigenesis through point mutation,

281 an give rise to RMS, cooperated with loss of p16INK4A to promote extended proliferation.

282 Germline mutations of CDKN2A that affect the p16INK4a transcript have been identified in numerous mel

283 Expression of the p16INK4a transcript is enriched in purified islets compa

284 regulator proteins CDK10, p120, p21CIP1, and p16INK4A; transcription factors/regulators Pax-5 and Id-

285 tributed to the expression of Ets-1, a known p16INK4a transcriptional activator, as well as unknown I

286 s also generated from frameshifted p14ARF or p16INK4a transcripts that were isolated from two additio

287 rotein, but instead blocks the expression of p16INK4a tumor suppressor gene.

288 The retinoblastoma (RB) and p16ink4a tumor suppressors are believed to function in a

289 The p16INK4a tumour suppressor accumulates in many tissues a

290 Silencing of tumor suppressor genes such as p16INK4a, VHL, and hMLH1 have established promoter hyper

291 p21WAF1 was observed in both cell types, but p16Ink4a was induced by ras only in fibroblasts.

292 When p16INK4a was induced for 6 days DNA synthesis remained s

293 Activation of p16INK4a was visualized in vivo using a murine strain th

294 Mice lacking p16Ink4a were born with the expected mendelian distribut

295 stant to cell cycle inhibition by PSM-RB and p16ink4a, which activates endogenous RB.

296 ction correlate with increased expression of p16INK4a, which encodes a cyclin-dependent kinase inhibi

297 s purpose, we exploited the transcription of p16INK4a, which rises dynamically with aging and correla

298 of cyclin-dependent protein kinases (CDKs), p16INK4a, whose loss has been related to the pathogenesi

299 y melanoma (MPM) without mutations affecting p16INK4A (wild-type p16INK4A); 191 probands from melanom

300 ion of endogenous RB and related proteins by p16ink4a yielded similar effects on enzyme expression.