ライフサイエンスコーパス: pVHL

1 ex containing the von Hippel-Lindau protein (pVHL).

2 stably expressing the wild-type VHL protein (pVHL).

3 finity binding to Von Hippel-Lindau protein (pVHL).

4 von Hippel-Landau tumour suppressor protein (pVHL).

5 n of the von Hippel-Lindau tumor suppressor (pVHL).

6 k is regulated by von Hippel-Lindau protein (pVHL).

7 s ubiquitination and degradation governed by pVHL.

8 of Spry2 and abrogated its interactions with pVHL.

9 as the most effective in refolding mutant of pVHL.

10 ibly via direct binding and stabilization of pVHL.

11 esting a potential link between U19/Eaf2 and pVHL.

12 the CTD allows the interaction of Rpb1 with pVHL.

13 omains is the least stable region in unbound pVHL.

14 ng c-src-mediated proteosomal degradation of pVHL.

15 teolytic degradation by the VHL gene product pVHL.

16 reinstates the interaction of HIF-1alpha and pVHL.

17 n of c-src and subsequent destabilization of pVHL.

18 ts in the von Hippel-Lindau tumor suppressor pVHL.

19 hat is stabilized by direct interaction with pVHL.

20 SPARC) and all were upregulated by wild-type pVHL.

21 er of the von Hippel-Lindau tumor suppressor pVHL.

22 e constitutively activated in the absence of pVHL.

23 both expressing misfolded versions of human pVHL.

24 regard to post-transcriptional regulation of pVHL.

25 nvasion and metastasis through its effect on pVHL.

26 ndidate renal tumor suppressor stabilized by pVHL.

27 the expression of Von Hippel Lindau protein (pVHL), a negative regulator of HIF, and that treatment w

28 These results demonstrate that pVHL acts to promote BIM(EL) protein stability in RCC ce

29 In cells lacking oxygen or functional pVHL, Akt was activated to promote cell survival and tum

30 Domain mapping analysis showed that the pVHL alpha-domain and the RACK1 WD 6-7 domains are criti

31 Overexpression of pVHL also increased activation of focal adhesion kinase

32 pVHL also reduced the stability of IGF1R mRNA via seques

33 pVHL also ubiquitylates the large subunit of RNA polymer

34 l staining revealed reduced concentration of pVHL and accumulation of KLF4 in breast cancer tissues.

35 D-arginine enhanced the ability of wild-type pVHL and certain misfolded mutant versions of pVHL to bi

36 he HIF binding site was shown to destabilize pVHL and decrease its binding affinity to HIF.

37 This interaction between pVHL and HIF is governed by post-translational prolyl hy

38 xia; thus, we set out to investigate whether pVHL and HIF participate in the hypoxia-mediated degrada

39 Codeletion of pVHL and HIF-2alpha in JG cells completely prevented the

40 munohistochemical staining revealed elevated pVHL and reduced KLF4 levels in colon cancer tissues.

41 ts suggest that specific association between pVHL and the hydroxylated HIF-alpha requires both the L1

42 proliferation of fibroblasts overexpressing pVHL and those cells were more resistant to the inhibiti

43 Von Hippel Lindau protein (pVHL) and hypoxia inducible factor (HIF) are key mediato

44 ygen requires the protein von Hippel-Lindau (pVhl) and pVhl disruption results in constitutive Hif ac

45 von Hippel-Lindau tumor suppressor protein (pVHL) and the hypoxia inducible factor (HIF) transcripti

46 al epithelium, emphasizing the importance of pVHL as a controller of mitotic fidelity in vivo.

47 U19/Eaf2 stabilizes pVHL, as shown by protein stability and pulse-chase stud

48 We identified Von Hippel-Lindau, pVHL, as the protein that governs KLF4 turnover in breas

49 that Spry2 acts as a scaffold to bring more pVHL/associated E3 ligase in proximity of HIF1alpha and

50 consensus destruction (D) box sequences, and pVHL associates with Cdh1, an activator of the anaphase-

51 We found that pVHL associates with the NF-kappaB agonist Card9 but doe

52 We establish that pVHL binds to Tat-binding protein-1 (TBP-1), a component

53 The von Hippel-Lindau protein (pVHL) bound directly to hydroxylated Akt and inhibited A

54 d was suppressed by full-length VHL protein (pVHL) but only partially by truncated VHL lacking the Sp

55 In cells with suppression of pVHL by short hairpin RNA, the Na-K-ATPase was not degra

56 These results demonstrate that a loss of pVHL can induce growth arrest in certain cells types, wh

57 pVHL can recruit VHLaK to repress HIF-1alpha transcripti

58 Therefore pVHL can serve as an adaptor for both a ubiquitin conjug

59 nctions of the VHL tumor suppressor protein (pVHL) can contribute to tumor initiation and progression

60 alpha levels in normoxia and hypoxia in both pVHL-competent and -deficient cells, whereas HAF knockdo

61 pVHL competes with IGF-I receptor (IGF-IR) for binding t

62 pVHL confers substrate specificity to the E3 ligase comp

63 oteins is essential for their recognition by pVHL containing ubiquitin ligase complexes and subsequen

64 pVHL contains consensus destruction (D) box sequences, a

65 However, it is unknown whether pVHL contributes to pulmonary fibrosis.

66 destabilization of BIM(EL) in the absence of pVHL contributes to the increased resistance of VHL-null

67 von Hippel-Lindau tumour suppressor protein (pVhl) controls hypoxia-inducible transcription factor (H

68 Loss of Jade-1 stabilization by pVHL correlates with renal cancer risk, making the relat

69 The interaction of Jade-1 and pVHL correlates with renal cancer risk.

70 pVHL-defective clear cell renal cell carcinoma cell line

71 nical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an on-

72 portant role in promoting tumor formation by pVHL-defective renal carcinoma cells among the three HIF

73 pVHL-defective renal carcinoma cells exhibit increased N

74 targets IGBP3 and PAI-1 are overproduced by pVHL-defective renal carcinoma cells.

75 a indicate that HIF plays a critical role in pVHL-defective tumor formation, raising the possibility

76 Decreased clusterin secretion by pVHL-defective tumors was confirmed in vivo by immunohis

77 Sustained hypoxia or HIF induction by pVHL deficiency inhibits mTOR complex 1 (mTORC1) activit

78 In pVHL-deficient cells, hypoxia did not decrease the Na-K-

79 tively activated in and drives the growth of pVHL-deficient clear cell RCCs.

80 at conditional inactivation of Hif-2alpha in pVHL-deficient mice suppressed hepatic Epo and the devel

81 pVHL-deficient RCC cells also demonstrate elevated PI3K/

82 Upon IGF-I stimulation, pVHL-deficient RCC cells exhibit increased RACK1/IGF-IR

83 Importantly, pVHL-deficient RCCs are dependent upon JNK activity for

84 pendent JNK hyperactivation is unique to the pVHL-deficient state.

85 nding regulator TRAP, and the hypoxia factor pVHL define a recognition module for peptides and nuclei

86 D box-independent pVHL degradation was also detected, indicating that othe

87 her ubiquitin ligases are also activated for pVHL degradation.

88 of HIF1alpha by a von Hippel-Lindau protein (pVHL)-dependent mechanism.

89 STRA13 is a pVHL-dependent bHLH transcription factor up-regulated on

90 tes HIF-1alpha prolyl hydroxylation and thus pVHL-dependent degradation of HIF-1alpha.

91 enhancing HIF-1alpha hydroxylation and thus pVHL-dependent degradation of HIF-1alpha.

92 e factor 1alpha and 2alpha, tagging them for pVHL-dependent polyubiquitination and proteasomal degrad

93 insights into KLF4 degradation and show that pVHL depletion in colorectal cancer cells leads to cell-

94 Overexpression of pVHL did not alter hypoxia-inducible factor luciferase r

95 Experimentally, type 2B pVHL disease mutant Y98N at the HIF binding site was sho

96 res the protein von Hippel-Lindau (pVhl) and pVhl disruption results in constitutive Hif activation.

97 observed that the interface between the two pVHL domains is the least stable region in unbound pVHL.

98 d with PHD1-3 and von Hippel-Lindau protein (pVHL) during normoxia but not in hypoxia.

99 y correlated with a gradient of VHL protein (pVHL) dysfunction in hypoxia signaling pathways.

100 ation of Na-K-ATPase required the functional pVHL E3 ligase and Ubc5 since pVHL mutants and dominant-

101 ) of HIF-1alpha trigger its association with pVHL E3 ligase complex, leading to HIF-1alpha degradatio

102 beta-domains responsible for assembling the pVHL E3 ubiquitin ligase complex and for recognizing the

103 Drosophila expressing misfolded versions of pVHL either L- or D-arginine rich diet rescued their let

104 xylase mediated hydroxylation and subsequent pVHL-elicited ubiquitylation of Spry2 target it for degr

105 ding sites, successfully stabilized the Y98N pVHL-elongin C complex and lowered the binding free ener

106 However, it is unclear whether pVHL exerts these mitotic regulatory functions in vivo a

107 Directly inhibiting BIM(EL) expression in pVHL-expressing RCC cells caused a similar decrease in c

108 induced cell cycle arrest is associated with pVHL expression in RCC cells.

109 e RACK1 expression level is not regulated by pVHL expression status, suggesting that pVHL modifies RA

110 Suppressing pVHL expression with RNA interference resulted in a decr

111 G1, Cdh1 downregulation results in increased pVHL expression, whereas Cdh1 overexpression results in

112 eas Cdh1 overexpression results in decreased pVHL expression.

113 t on PLD in renal cancer cells with restored pVHL expression.

114 ted that estrogen-induced down-regulation of pVHL facilitates accumulation of KLF4.

115 /Eaf2 and both the alpha and beta domains of pVHL for this binding.

116 pVHL forms a ternary complex with elongin C and elongin

117 pVHL forms part of the E3 ubiquitin ligase complex that

118 ked to classical VHL disease compromise this pVHL function although some missense mutations result in

119 serves as a direct mediator between loss of pVHL function and enhanced IGF-IR signaling pathway in R

120 er, although the effects of this mutation on pVHL function are not fully understood.

121 n hypoxia-inducible factor (HIF)-independent pVHL function formed the basis for selectivity.

122 ear to function cooperatively with a loss of pVHL function in tumorigenesis.

123 losteric effects of these mutants may rescue pVHL function in von Hippel-Lindau disease.

124 ible factor (HIF)-alpha subunits and loss of pVHL function leads to HIF stabilization.

125 The significance for pVHL function of two further genes upregulated by wild-t

126 Loss of pVHL function results in constitutive activation of HIF-

127 n is a secreted marker for a HIF-independent pVHL function that might be especially important in pheo

128 tially compared with isogenic cells in which pVHL function was restored.

129 (as a result of kidney-specific ablation of pVHL function) were reverted in vivo also by genetic inh

130 ed target peptide, reflecting restoration of pVHL function.

131 cells related to: tumor suppressor protein (pVHL) function, the histone acetylation dependence upon

132 rting the novel and intriguing findings that pVHL has a crucial role in endochondral bone development

133 We show that pVHL has a decreased half-life in G1, Cdh1 downregulatio

134 ng in VHL disease and can be rationalized if pVHL has functions separate from its control of HIF.

135 The VHL protein (pVHL) has been implicated in many cellular activities in

136 The VHL gene product, pVHL, has multiple functions including directing the pol

137 In the absence of pVHL, HIF becomes stabilized and is free to induce the e

138 the coordination of internal motions of the pVHL.HIF-1alpha complex.

139 Moreover, dynamic organization of pVHL.HIF-1alpha recognition is focally centered on Gln(1

140 We recently reported inhibitors of the pVHL:HIF-1alpha interaction, however they exhibited mode

141 We found that in the presence of pVHL hypoxia decreased Na-K-ATPase activity and promoted

142 yltransferase activity that is stabilized by pVHL in a manner that correlates with risk of VHL renal

143 ients with IPF expressed increased levels of pVHL in fibroblastic foci.

144 alpha is not recognized and ubiquitinated by pVHL in IPMK KO (knockout) cells.

145 Bleomycin treatment also induced pVHL in lung fibroblasts, but not in alveolar type II ce

146 ta provide direct evidence for a key role of pVHL in mediating oriented cell division and faithful mi

147 e found that renin cell-specific deletion of pVHL in mice leads to a phenotype switch in JG cells, fr

148 Mice lacking pVHL in osteoblasts with constitutive HIF-1alpha activat

149 sights into the role of the tumor suppressor pVHL in oxygen sensing motivated the testing of drugs th

150 Although the involvement of pVHL in oxygen sensing through targeting hypoxia-inducib

151 We thus propose that suppression of pVHL in response to estrogen signaling results in elevat

152 In order to investigate the role of pVhl in T-cell development, we generated mice with thymo

153 Inactivation of pVhl in the mouse germ line results in embryonic lethali

154 key regulatory role for the tumor suppressor pVHL in the regulation of the vascular system and normal

155 t deletion of the von Hippel-Lindau protein (pVHL) in juxtaglomerular (JG) cells of the kidney suppre

156 ion of the wild-type protein encoded by VHL (pVHL) in tumors with biallelic VHL inactivation (VHL(-)(

157 tween the elongin C and HIF binding sites in pVHL, in the alpha- and beta-domains, respectively, medi

158 proteins, Skp2, Fbw7, beta-TrCP1, Cdc4, and pVHL, in two forms: bound to their substrates and bound

159 ncluding DOC-2/DAB2 and MLC2) the effects of pVHL inactivation and hypoxia were similar.

160 erally in renal cancer, perhaps initially by pVHL inactivation and subsequently by increased proteaso

161 o investigate the functional consequences of pVHL inactivation and the role of HIF signaling in renal

162 herefore, the pathological changes caused by pVHL inactivation in skin and liver are due largely to d

163 pVHL inactivation results in stabilization of the hypoxi

164 e closely phenocopied the changes seen after pVHL inactivation than did the HIF2alpha variant alone.

165 Hippel-Lindau tumor suppressor gene product (pVHL), including targeting the alpha subunits of the het

166 In addition, cells lacking wild-type pVHL, including cells producing type 2C pVHL mutants, we

167 Silencing of pVHL increased levels of Spry2 by decreasing its ubiquit

168 Overexpression of pVHL increased lung fibroblast proliferation, protein ab

169 receptor 2 (PAR2) (both downregulated by wt pVHL) increased cell growth and motility in a RCC cell l

170 , indicating that full in vivo expression of pVHL indeed requires U19/Eaf2.

171 High CSN5 expression generates a pVHL-independent form of CSN5 that stabilizes HIF-1 alph

172 nd ubiquitinates HIF-1alpha by an oxygen and pVHL-independent mechanism, thus targeting HIF-1alpha fo

173 f2 knockout mice expressed reduced levels of pVHL, indicating that full in vivo expression of pVHL in

174 In addition, overexpression of pVHL induced expression of the alpha5 integrin subunit.

175 ting its mRNA expression, and overexpressing pVHL inhibited BIM(EL) polyubiquitination.

176 for activated C kinase 1 (RACK1) is a novel pVHL-interacting protein.

177 Furthermore, reintroducing pVHL into RCC cells increased endogenous Jade-1 and supp

178 Reintroducing pVHL into VHL-null cells increased the half-life of BIM(

179 Under native conditions, free pVHL is a molten globule, but it is stabilized in the E3

180 Taken together, these results suggest that pVHL is a novel substrate of APC/C(Cdh1).

181 pVHL is a tumor-suppressor protein implicated in a varie

182 The von Hippel-Lindau tumor suppressor pVHL is an E3 ligase that targets hypoxia-inducible fact

183 Hippel-Lindau (VHL) tumor suppressor protein pVHL is commonly mutated in clear cell renal cell carcin

184 The von Hippel-Lindau (VHL) tumor suppressor pVHL is lost in the majority of clear-cell renal cell ca

185 that were highly similar to those seen when pVHL is lost in these organs.

186 Loss of pVHL is not sufficient, however, to cause ccRCC.

187 Type 2B mutant pVHL is predicted to be defective in hypoxia inducible f

188 a suggest that tight regulation of Hif-1 via pVhl is required for normal thymocyte development and vi

189 One function of pVHL is to regulate the stability of the hypoxia-inducib

190 von Hippel Lindau tumor suppressor protein (pVHL) is a component of a ubiquitin ligase that promotes

191 von Hippel-Lindau tumor-suppressor protein (pVHL) is associated with von Hippel-Lindau disease, an i

192 tumor suppressor von Hippel-Lindau protein (pVHL) is critical for cellular molecular oxygen sensing,

193 von Hippel-Lindau tumor suppressor protein (pVHL) is frequently mutated in kidney cancer and is part

194 von Hippel-Lindau tumor suppressor protein (pVHL) is one of these proteins.

195 The VHL tumor suppressor protein (pVHL) is part of an E3 ubiquitin ligase that targets HIF

196 The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3

197 ippel-Lindau (VHL) tumor suppressor protein (pVHL) is unique in that it is not associated with tumor

198 n of the von Hippel-Lindau tumor suppressor, pVHL, is associated with both hereditary and sporadic re

199 The VHL gene product, pVHL, is part of a ubiquitin ligase complex that targets

200 The VHL gene product, pVHL, is the substrate recognition unit of an ubiquitin

201 B-cell-specific depletion of pVHL leads to constitutive HIF stabilization, decreases

202 , that common oncogenic VHL mutations render pVHL less stable than the wild-type protein, distort its

203 SB1 protein level negatively correlates with pVHL level and metastasis-free survival in clinical samp

204 We found that pVHL levels decreased in hypoxia and that hypoxia-induce

205 pVHL levels fluctuate during the cell cycle, paralleling

206 ell differentiation in 20% O2; additionally, pVHL levels were modulated during the same time period.

207 Deprived of pVhl, livers accumulated tryglicerides and circulating k

208 the combined loss of Phd2 and Phd3 resembles pVHL loss appear to differ for different HIF-responsive

209 und that Ror2 was indeed associated with the pVHL loss in RCC as well as with VHL somatic mutations t

210 A multistep signaling pathway that links pVHL loss to JNK activation involves the formation of a

211 clear-cell RCC between PTEN inactivation and pVHL loss, which leads to decreased Jade-1 levels that s

212 target of the VHL ubiquitylating complex and pVHL may regulate angiogenesis by targeting hsRPB7 for d

213 roxylation and Ser5 phosphorylation of Rbp1, pVHL may regulate tumor growth.

214 (VHL(-)(/)(-)) suppresses tumorigenesis, and pVHL-mediated degradation of HIFalpha is necessary and s

215 pVHL-mediated degradation of Na-K-ATPase required the fu

216 1alpha), a protein typically regulated via a pVHL-mediated degradation pathway.

217 of reactive oxygen species was necessary for pVHL-mediated Na-K-ATPase degradation during hypoxia.

218 d by pVHL expression status, suggesting that pVHL modifies RACK1 functions independent of the VHL/elo

219 the functional pVHL E3 ligase and Ubc5 since pVHL mutants and dominant-negative Ubc5 prevented Na-K-A

220 pVHL mutants linked to familial pheochromocyctoma (type

221 sed vascularity and bone regeneration in the pVHL mutants were VEGF dependent and eliminated by conco

222 type pVHL, including cells producing type 2C pVHL mutants, were defective with respect to expression

223 We have expressed missense pVHL mutations in Vhl(-/-) murine embryonic stem cells t

224 of estrogen and show that elevated levels of pVHL or depletion of KLF4 attenuates the estrogen-induce

225 ell carcinoma (RCC) cells that either lacked pVHL or expressed pVHL through stable transfection were

226 These findings suggest that pVHL participates in the hypoxia-mediated degradation of

227 ort that the Von Hippel-Lindau gene product, pVHL, physically interacts with KLF4 and regulates its r

228 ese observations support the hypothesis that pVHL plays multiple roles in the cell, and that these ac

229 Moreover, suppression of pVHL prevented TGF-beta1-induced proliferation of mouse

230 hich the representative Type 2B R167Q mutant pVhl produces a unique profile of HIF dysregulation, the

231 The sensitivity of pVHL-proficient cells to these shRNAs was not restored u

232 tion of HIFalpha or restoration of wild-type pVHL protein expression has not proved readily feasible,

233 The mechanism by which pVHL protein functions in renal tumor suppression remain

234 ls and increased the half-life of the mutant pVHL proteins in the cell culture.

235 The polycystin-1 (PC1) and pVHL proteins may therefore participate in the same key

236 All mutant pVHL proteins restored proper hypoxic regulation of HIF1

237 l line expressing a Type 1 or Type 2B mutant pVHL (RCC-associated) to those of a Type 2A or 2C mutant

238 lyl hydroxylation, which is prerequisite for pVHL recognition, is interrupted in IPMK-deleted cells.

239 4 VHL-/- cells compared with their wild-type pVHL-reconstituted counterparts.

240 to coordinate dynamic coupling among distant pVHL regions, whose mutational disruption inactivates VH

241 Here we report that in RCC cells, pVHL regulates expression of Rpb1 and is necessary for l

242 pVHL regulates the protein stability of hypoxia-inducibl

243 The von Hippel-Lindau tumor suppressor pVHL regulates the stability of hypoxia-inducible factor

244 pVHL regulation of CDKN1C, SPARC and GNG4 was not mimick

245 exogenous fibronectin, which indicates that pVHL regulation of fibronectin deposition plays an impor

246 as been well documented, less is known about pVHL regulation under both normoxic and hypoxic conditio

247 documented function of the VHL gene product (pVHL) relates to its ability to polyubiquitinate, and he

248 Introducing a pVHL-resistant hypoxia-inducible factor 1alpha (HIF1alph

249 interaction with von Hippel-Lindau protein (pVHL), resulting in HIF-1alpha degradation.

250 von Hippel-Lindau tumor suppressor protein (pVHL), resulting in the accumulation of hypoxia-inducibl

251 Loss of pVHL results in constitutive activation of the transcrip

252 results indicate that elevated expression of pVHL results in the aberrant fibronectin expression, act

253 This work reveals a new mechanism of pVHL's regulation by which cancer acquires invasiveness

254 Instead, pVHL serves as an adaptor that promotes the phosphorylat

255 Therefore, the pVHL-SFMBT1-SPHK1 axis serves as a potential therapeutic

256 Arginine treatment increased pVHL solubility in both models and increased the half-li

257 Our simulations showed that the decrease in pVHL stability and binding affinity are allosterically r

258 x with elongin C and elongin B, critical for pVHL stability and function, which interacts with Cullin

259 The discovery of the PHD-HIF-pVHL system revolutionized our fundamental understanding

260 rain tumor domains 1 (SFMBT1) as a candidate pVHL target.

261 We identified 30 differentially regulated pVHL targets (26 of which were 'novel') and the results

262 pVHL targets alpha subunits of the heterodimeric transcr

263 As the identification of novel pVHL targets might provide insights into pVHL tumour sup

264 The von Hippel-Lindau gene product (pVHL) targets the alpha subunit of basic helix-loop-heli

265 The von Hippel-Lindau (VHL) gene product, pVHL, targets the alpha subunit of the hypoxia-inducible

266 henocopy of the changes seen in mice lacking pVHL than the loss of Phd2 alone.

267 tatus of the von Hippel-Lindau gene product (pVHL) that is responsible for HIF-1alpha degradation and

268 Second, in pVHL (the protein encoded by the VHL gene)-deficient ccR

269 ) cells that either lacked pVHL or expressed pVHL through stable transfection were used to prepare RN

270 protein 1 (WSB1) is a negative regulator of pVHL through WSB1's E3 ligase activity.

271 The VHL tumor suppressor protein (pVHL), through its oxygen-dependent polyubiquitylation o

272 hydroxylation and subsequent recognition by pVHL, thus leading to Akt hyperactivation.

273 ions that directly compromise the ability of pVHL to assemble the E3 or to contact the substrate.

274 VHL and certain misfolded mutant versions of pVHL to bind ODD, the HIF-derived target peptide, reflec

275 which promotes Card9 phosphorylation, links pVHL to control of NF-kappaB activity and tumorigenesis.

276 We first examined the ability of mutant pVHL to direct degradation of the hypoxia inducible fact

277 The binding of pVHL to HIFalpha requires that HIFalpha be hydroxylated

278 , binds both the CODD of HIF-1 alpha and the pVHL tumor suppressor.

279 hibit inactivation of the von Hippel-Lindau (pVHL) tumor suppressor, establishing it as the major und

280 vel pVHL targets might provide insights into pVHL tumour suppressor activity, we performed gene expre

281 t and HIF-independent mechanisms account for pVHL tumour suppressor activity.

282 These provide insights into mechanisms of pVHL tumour suppressor function and identify novel hypox

283 er, is usually linked to inactivation of the pVHL tumour suppressor protein and consequent accumulati

284 Mechanistically, WSB1 promotes pVHL ubiquitination and proteasomal degradation, thereby

285 gene, many of which render the VHL protein (pVHL) unstable.

286 Because Spry2 can also associate with pVHL, using a mutant form of Spry2 (3P/3A-Spry2) that bi

287 We therefore propose that unexpectedly pVHL, via the degradation of KLF4, is a facilitating fac

288 Because pVHL (von Hippel-Lindau protein) directs the proteolysis

289 IF-1alpha is constitutively ubiquitinated by pVHL (von Hippel-Lindau protein) followed by proteasomal

290 f two further genes upregulated by wild-type pVHL was initially unclear, but re-expression of GNG4 (G

291 (3P/3A-Spry2) that binds HIF1alpha, but not pVHL, we show that WT-Spry2, but not the 3P/3A-Spry2 dec

292 Fibroblasts overexpressing pVHL were more sensitive to RGD peptide-mediated reducti

293 s showed an association between U19/Eaf2 and pVHL, whereas deletion mutagenesis revealed the requirem

294 he von Hippel-Lindau (VHL) tumor suppressor (pVHL), which inhibits ubiquitylation and degradation of

295 of HIF-1alpha is von Hippel-Lindau protein (pVHL), which mediates the oxygen-dependent, proteasomal

296 ions designed to stabilize unbound wild-type pVHL, which are away from the elongin C and HIF binding

297 control of AKT/AKT1 in RCC, through loss of pVHL, which decreases Jade-1 protein, or through attenua

298 on of the von Hippel-Lindau tumor suppressor pVHL, which targets both HIFs for proteasomal degradatio

299 mplex and lowered the binding free energy of pVHL with HIF.

300 This is initial evidence that pVHL, without any genetic alteration, can be regulated b