ライフサイエンスコーパス: VHL

1 VHL and HIF regulate the balance between glycolysis and

2 VHL binding inhibits BIM-EL phosphorylation by extracell

3 VHL inactivation results in the constitutive activation

4 VHL is a potential target for treating anemia and ischem

5 VHL is expressed as two variants, VHL30 and VHL19.

6 VHL knockout nephron progenitors also exhibit persistent

7 VHL loss activates the HIF-2 transcription factor, and c

8 VHL mutants fail to bind hydroxylated BIM-EL, regardless

9 VHL mutation and hypoxia-inducible factor 1alpha express

10 VHL-based degraders could be optimized from suboptimal c

11 VHL-mutant cells exhibit metabolic abnormalities that ca

12 efined tumors were identified, including 286 VHL-deficient, 91 FLCN-deficient, 52 MET-activated, and

13 While type 1, 2A, and 2B VHL mutants are defective in regulating HIFalpha, type 2

14 (89)Zr-bevacizumab PET visualized 59 VHL manifestations, 0-17 per patient.

15 r diameter-based surveillance protocol and a VHL genotype and tumor diameter-based algorithm (a tailo

16 is targeting chimeras (PROTACs) containing a VHL ligand can hijack the E3 ligase activity to induce d

17 and selectively degraded MEK1 and MEK2 in a VHL E3 ligase- and proteasome-dependent manner and suppr

18 contrast to its hypoxia-regulated activity, VHL mono-, rather than poly-ubiquitinates AURKA, in a PH

19 more effective for the treatment of advanced VHL-associated RCH.

20 Three patients with advanced VHL-associated juxtapapillary RCH were treated with syst

21 Three patients with advanced VHL-related juxtapapillary RCH treated with systemic sun

22 stress as an underlying vulnerability of all VHL mutated renal cancers that could be therapeutically

23 yclin-dependent kinases 4 and 6 (CDK4/6) and VHL inactivation in two species (human and Drosophila) a

24 ied an inverse correlation between Daam2 and VHL expression across a host of cancers, including gliom

25 We report that VHL-deficient and VHL-positive renal cancer cells possess significantly de

26 thetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation.

27 Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients.

28 s display strong tissue specificity (such as VHL in kidney cancer samples and GATA3 in breast cancer

29 d VHL, is a promising approach to augmenting VHL levels and function.

30 ic to platelets than ABT263 in vitro because VHL is poorly expressed in platelets.

31 ified a synthetic lethal interaction between VHL and the m(6)A RNA demethylase FTO in renal cell carc

32 ker analyses revealed a relationship between VHL mutation status and outcome with everolimus but not

33 nsitive function of VHL that is abolished by VHL type 2C mutations.

34 roxylated by EglN3 and subsequently bound by VHL.

35 VEGF, for the treatment of cancers caused by VHL inactivation, such as clear-cell renal cell carcinom

36 le range [IQR], 0.57-0.68 cm/y), followed by VHL-deficient tumors (GR, 0.37 cm/y; IQR, 0.25-0.57 cm/y

37 gh glucose induces ubiquitination of G6PD by VHL E3 ubiquitin ligase, which leads to ROS accumulation

38 that the two major species are generated by VHL protein cleavage, and the cleavage regulates VHL pro

39 X - caspase-3 pathway unrelated to canonical VHL pathway.

40 ession analysis revealed that in Th17 cells, VHL regulates many cellular pathways, including genes en

41 We characterized VHL species using genetical and pharmacological approach

42 Nedd8 conjugated VHL is unable to bind to p53 thereby preventing the indu

43 Compared with controls, VHL knockout kidneys are smaller and developmentally del

44 with wild-type p53 than was a corresponding VHL-utilizing PROTAC with similar potency and efficacy t

45 CRL2(VHL) ligase complex regulates HIF-1alpha protein levels

46 a, through MUL1 ligase, can inhibit the CRL2(VHL) complex leading to high HIF-1alpha protein levels a

47 fied UBXN7, the cofactor protein of the CRL2(VHL) ligase complex, as a specific substrate of MUL1 lig

48 tochondria and operates upstream of the CRL2(VHL) ligase complex.

49 VHL E3 ubiquitin ligase, ECV (Elongins/Cul2/VHL).

50 Using proteomic analysis of the Daam2-VHL complex coupled with conditional genetic knockout mo

51 ons in patients of African origin, decreased VHL and PBRM1 mutations in renal cancer patients of Afri

52 IF-2alpha inhibition in HIF-2alpha-dependent VHL(-/-) ccRCC cells and not antagonistic with HIF-2alph

53 The most active compound, CM11, dimerizes VHL with high avidity in vitro and induces potent, rapid

54 Von Hippel-Lindau disease (VHL) is one of the most common inherited neoplasia syndr

55 the VHL ubiquitin ligase complex, displaces VHL-associated Cullin 2, and impairs HIF2alpha ubiquityl

56 ministering L- or D-arginine to a Drosophila VHL model and to human renal carcinoma cells, both expre

57 To explore VHL as a regulator defining nephron progenitor self-rene

58 l for high-risk cohorts such as the familial VHL disease patients.

59 Here we identified a novel mechanism for VHL suppression in tumors that do not have inactivating

60 Our findings identify a novel role for VHL in mediating nephron progenitor differentiation thro

61 ) is a novel, hypoxia-independent target for VHL ubiquitination.

62 Furthermore, genetic testing for VHL is indicated in some individuals with seemingly spor

63 ibitors represent potential therapeutics for VHL-deficient CC-RCC.

64 examined as a potential novel treatment for VHL cancer syndrome.

65 of TNFalpha associated with VHL loss forced VHL-deficient cells to rely on intact RIPK1 to inhibit a

66 African American patients have less frequent VHL inactivation, are enriched in the ccB molecular subt

67 n slowing progression of ocular disease from VHL-associated RCH.

68 -5p expression in the presence of functional VHL-wt protein under a normoxic condition, which might t

69 he von Hippel-Lindau tumour suppressor gene (VHL).

70 aused by a loss or mutation in a single gene,VHL, but it exhibits a wide phenotypic variability that

71 40% of CNS hemangioblastoma harbor germline VHL mutations without a family history or additional fea

72 lterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymou

73 Some germline VHL mutations cause familial pheochromocytoma and encode

74 ntly less likely than white patients to have VHL mutations (2 of 12 [17%] vs 175 of 351 [50%], respec

75 l-Lindau (VHL)-associated hemangioblastomas (VHL-HB) arise in the central nervous system (CNS), and a

76 Our results illustrate how VHL and PBRM1 co-operate to drive renal transformation a

77 In this study, we hypothesized VHL negatively regulates Th17 differentiation and deleti

78 Together, these data identify VHL as an E3 ligase with important cellular functions un

79 nkers, which resulted in two novel, improved VHL-recruiting MEK1/2 degraders, 24 (MS928) and 27 (MS93

80 tologic expression of SSTR1, 2a, 4, and 5 in VHL-HBs.

81 tin analogue octreotide induces apoptosis in VHL-HB stromal cells in a dose-dependent fashion by BAX

82 markedly enhanced induction of apoptosis in VHL-null 786-O cells but not in VHL wild-type Caki-2 cel

83 e complex genotype/phenotype correlations in VHL disease remain unknown.

84 eutic approaches targeting VHL deficiency in VHL diseases.

85 Mice deficient in VHL in their T cells were resistant to an autoimmune dis

86 d somatostatin receptor (SSTR) expression in VHL-HBs, offering an alternative therapeutic strategy.

87 n vitro Th17 differentiation was impaired in VHL-deficient T cells.

88 Moreover, FTO expression is increased in VHL-deficient ccRCC tumors compared to normal adjacent t

89 leading cause of morbidity and mortality in VHL disease.

90 Mutations in VHL and alterations in its downstream pathways are the m

91 pathways that drive cancer, but mutations in VHL are restricted to limited subsets of malignancies.

92 We also show that analysis of mutations in VHL using our workflow provides valuable insights into t

93 Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (V

94 ation triggered rapid programmed necrosis in VHL-deficient cell lines and primary ccRCC tumor cells,

95 apoptosis in VHL-null 786-O cells but not in VHL wild-type Caki-2 cells.

96 and increased ROS in VHL-/- cells but not in VHL+/+ cells, which utilized glucose oxidation for gluta

97 es and primary ccRCC tumor cells, but not in VHL-restored counterparts.

98 d EGFR, whereas frameshifts are prevalent in VHL, GATA3, TP53, ARID1A, PTEN and ATRX.

99 wever, the precise mechanisms of AR roles in VHL wild-type (VHL-wt) ccRCC, remain unclear.

100 rs depleted pyrimidines and increased ROS in VHL-/- cells but not in VHL+/+ cells, which utilized glu

101 uncal mutations in ccRCC, including those in VHL, SET2, PBRM1 and BAP1, may engender genomic instabil

102 ive HIF-2 activity restores tumorigenesis in VHL-reconstituted ccRCC cells.

103 lesions in known RCC driver genes, including VHL, a common initiating clear cell RCC (ccRCC) genetic

104 ment of cellular ascorbate levels, increased VHL binding, and decreased HIF-1alpha stability.

105 ple pathways, including the ccRCC-initiating VHL-HIF2A pathway.

106 Unexpectedly, cell-intrinsic VHL-Hif1alpha pathway activation also delays the timing

107 4 cells and RCC4VHL cells with re-introduced VHL.

108 Von Hippel-Landau (VHL) protein is a potent tumor suppressor regulating num

109 Here we show that the E3 ligase VHL interacts with Daam2 and their mutual antagonism reg

110 Von Hippel Lindau (VHL) is a tumour suppressor that is lost in the majority

111 Loss of von Hippel Lindau (VHL) protein function is a key driver of VHL diseases, i

112 ir deemed unsuitable: the von Hippel-Lindau (VHL) and BRD9, a bromodomain-containing subunit of the S

113 AR studies exploring both von Hippel-Lindau (VHL) and cereblon (CRBN) E3 ligase ligands and a variety

114 ferent ligands recruiting Von Hippel-Lindau (VHL) and cereblon (CRBN) E3 ubiquitin ligases, our strat

115 the tumor suppressor gene von Hippel-Lindau (VHL) are major causes of clear-cell renal cell carcinoma

116 von Hippel-Lindau (VHL) disease is a rare familial cancer predisposition sy

117 mas (RCH) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an

118 t targets BCL-X(L) to the Von Hippel-Lindau (VHL) E3 ligase for degradation.

119 ances of a ligand for the von Hippel-Lindau (VHL) E3 ligase.

120 he functional loss of the von Hippel-Lindau (VHL) gene occurs in 90% of CC-RCC, driving cancer progre

121 von Hippel-Lindau (VHL) is a critical tumor suppressor in clear cell renal

122 egulated tumor-suppressor von Hippel-Lindau (VHL) is an E3 ligase that recognizes its substrates as p

123 Von Hippel-Lindau (VHL) is an E3 ubiquitin ligase that targets proteins, in

124 von Hippel-Lindau (VHL) patients develop multiple central nervous system he

125 von Hippel-Lindau (VHL) protein is known to destabilize myogenin via the ub

126 We found that the von Hippel-Lindau (VHL) protein, an E3 ubiquitin ligase subunit, directly b

127 lation of HIFalpha by the von Hippel-Lindau (VHL) protein, the mechanisms underlying the complex geno

128 eting cereblon (CRBN) and Von Hippel-Lindau (VHL) proteins.

129 ease independent of their von Hippel-Lindau (VHL) status.

130 The von Hippel-Lindau (VHL) syndrome is a rare inherited cancer, caused by muta

131 eillance of patients with von Hippel-Lindau (VHL) syndrome.

132 ssion is regulated by the von Hippel-Lindau (VHL) tumor suppressor and is highly expressed in clear c

133 mTORC1 in the absence of von Hippel-Lindau (VHL) tumor suppressor expression.

134 The von Hippel-Lindau (VHL) tumor suppressor gene is inactivated in the majorit

135 ), cells deficient in the von Hippel-Lindau (VHL) tumor suppressor gene use glutamine to generate cit

136 Loss of the von Hippel-Lindau (VHL) tumor suppressor is a hallmark feature of renal cle

137 , loss of function of the von Hippel-Lindau (VHL) tumor suppressor, provides a human pathogenesis mod

138 molecular constraints on von Hippel-Lindau (VHL) ubiquitin ligase tumor suppressor function.

139 complex subunits B and D, von Hippel-Lindau (VHL), RET, and neurofibromin 1 (NF1).

140 ng the growth kinetics of Von Hippel-Lindau (VHL)-associated clear cell renal cell carcinoma (ccRCC)

141 Von Hippel-Lindau (VHL)-associated hemangioblastomas (VHL-HB) arise in the

142 regulated by hypoxia in a von Hippel-Lindau (VHL)-dependent manner both in RCC cell culture and clini

143 h rises at birth, and the von Hippel-Lindau (VHL)-hypoxia-inducible factor 1alpha (Hif1alpha) pathway

144 Von Hippel-Lindau (VHL)-null 786-O, RCC4 and A498 Renal Cell Carcinoma (RCC

145 reported a first-in-class von Hippel-Lindau (VHL)-recruiting mitogen-activated protein kinase kinases

146 h is largely regulated by von Hippel-Lindau (VHL; a protein component of a ubiquitin ligase complex)

147 Thus, the Mdm2-VHL interaction represents a pathway that impacts tumor

148 effect against Y-27632 treatment, mimicking VHL reintroduction.

149 Moreover, VHL-deficient cells that expressed activating mTOR mutan

150 is of VHL, especially missense point-mutated VHL, is a promising approach to augmenting VHL levels an

151 Multiple somatic mutations (VHL, PBRM1, SETD2, KDM5C, TP53, BAP1, PTEN, MTOR) were a

152 tools to probe the VHL-HIF pathways and new VHL ligands for next-generation PROTACs.

153 ing the use of systemic sunitinib for ocular VHL lesions during a period of 9 months.

154 tively reduced the colony-forming ability of VHL-deficient CC-RCC, thus mimicking the effect of Y-276

155 In the absence of VHL, Th17 cells had decreased activation of STAT3 and SM

156 Codeletion of VHL together with HIF2A but not with HIF1A led to appare

157 and proteasome-dependent self-degradation of VHL in different cell lines, in a highly isoform-selecti

158 generate mice with a conditional deletion of VHL from Six2(+) nephron progenitors.

159 gulates Th17 differentiation and deletion of VHL in CD4 T cells would elevate HIF-1alpha and increase

160 CH1 in mice with tubule-specific deletion of VHL led to dysplastic hyperproliferation of tubular epit

161 acts on the ccRCC metastatic destinations of VHL-wt ccRCC cells under different oxygen conditions.

162 s required for binding to the beta domain of VHL and polyubiquitylation via ECV, leading to increased

163 l therapeutic targets in ccRCC downstream of VHL loss besides hypoxia-inducible factor 2alpha (HIF2al

164 au (VHL) protein function is a key driver of VHL diseases, including sporadic and inherited clear cel

165 pubescin as a novel agent for elimination of VHL-null RCC cells via apoptosis is warranted for furthe

166 nt to explain the observed distinct fates of VHL-deficient and restored cells.

167 t a family history or additional features of VHL disease.

168 mark of ccRCC is genetic loss-of-function of VHL (von Hippel-Lindau) that leads to a highly vasculari

169 e identified an oxygen-sensitive function of VHL that is abolished by VHL type 2C mutations.

170 he-art information regarding the genetics of VHL and will serve as a key reference for nongenetics pr

171 th GLS1 inhibitors to suppress the growth of VHL-/- cells in vitro and in vivo.

172 ase checkpoint, and suppressed the growth of VHL-/- RCC cells.

173 Mutational inactivation of VHL is the earliest genetic event in the majority of cle

174 ression in renal cancer cells independent of VHL status.

175 Here, we show that loss of VHL alone results in DNA replication stress and damage a

176 Our findings indicate that loss of VHL could be driving tumour cell dissemination through s

177 here, although key mutations such as loss of VHL is an almost ubiquitous finding, there remains a con

178 nthetic lethal interactions with the loss of VHL through analysis of primary tumor genomic and transc

179 The majority of VHL mutations are private, but there are also well-chara

180 important roles in modulating metastasis of VHL-mutant clear cell renal cell carcinoma (ccRCC).

181 acted with VHL to modulate the metastasis of VHL-wt ccRCC via an oxygen-dependent manner.

182 wed that a CRISPR/Cas9-mediated knock out of VHL in the RENCA model leads to morphologic and molecula

183 ntified FTO as a synthetic lethal partner of VHL because deletions of FTO are mutually exclusive with

184 Modulation of the proteostasis of VHL, especially missense point-mutated VHL, is a promisi

185 predictive potential for the growth rate of VHL-associated ccRCC.

186 ered similar metabolic changes regardless of VHL status, suggesting that metabolic responses alone ar

187 omote angiogenesis through the regulation of VHL.

188 , many details underlying the regulations of VHL proteostasis are unknown.

189 ired for the increased CDK4/6 requirement of VHL(-/-) ccRCC cells.

190 The role of VHL in Th17 cells is not known.

191 However, the role of VHL loss of function in the development of ccRCC via inf

192 and group-based optimization of a series of VHL inhibitors with low nanomolar potencies and improved

193 However, how these multiple species of VHL are generated and whether the process regulates VHL

194 pmental myelination through stabilization of VHL via K63-linked ubiquitination.

195 otes metabolic reprogramming and survival of VHL-deficient ccRCC cells.

196 lectively reduces the growth and survival of VHL-deficient cells in vitro and in vivo.

197 e factor alpha, a well established target of VHL E3 ubiquitin ligase, ECV (Elongins/Cul2/VHL).

198 ied and validated for selective targeting of VHL-deficient CC-RCC in multiple genetic backgrounds by

199 dent therapeutic target for the treatment of VHL-deficient renal cell carcinoma.

200 However, the predictive value of VHL mutations has been questioned.

201 Tumor-associated variants of VHL differentiate between these two functions, as a path

202 g FTO as an HIF-independent vulnerability of VHL-deficient cancers.

203 mpounds (LOPAC), was screened in parallel on VHL-deficient RCC4 cells and RCC4VHL cells with re-intro

204 Our experience and previous reports on VHL-HB avidity to somatostatin analogues suggested somat

205 and in vitro analyses, that common oncogenic VHL mutations render pVHL less stable than the wild-type

206 eration, including cancers harboring IDH1 or VHL mutations, suggesting multiple mechanisms for pathwa

207 it alternate mutation profiles: VHL-PBRM1 or VHL-BAP1.

208 ithin a region that is important for the p53-VHL interaction.

209 between these two functions, as a pathogenic VHL mutant that retains intrinsic ability to ubiquitinat

210 se effects did not involve the classical PHD/VHL pathway for HIF upregulation, but instead involved t

211 nt followed by three early departure points: VHL and PBRM1 mutations, del(14q) and other somatic copy

212 Here we disclose VH298, a potent VHL inhibitor that stabilizes HIF-alpha and elicits a hy

213 K1, resulting in a kinase unable to preserve VHL function and lacking glioma suppression activity.

214 4.1R may influence myogenesis by preventing VHL-mediated myogenin degradation.

215 nificantly increased in cultured and primary VHL loss-of-function kidney cells.

216 rs that exhibit alternate mutation profiles: VHL-PBRM1 or VHL-BAP1.

217 Lastly, we explore the p38delta:PROTAC:VHL complex to explain the different selectivity profile

218 are mutations in genes including TP53, PTEN, VHL, EGFR, and FBXW7 and 99 medium-recurrence mutations

219 hs, these two PROTACs differentially recruit VHL, resulting in degradation of p38alpha or p38delta.

220 protein cleavage, and the cleavage regulates VHL proteostasis and subsequent function.

221 generated and whether the process regulates VHL proteostasis and function are unknown.

222 r study reveals a novel mechanism regulating VHL proteostasis and function, which is significant for

223 t to define an upstream mechanism regulating VHL suppression in cancer and describe the role of Daam2

224 ng elevation in TNFalpha expression rendered VHL-deficient cells susceptible to necrosis triggered by

225 ctor PBRM1 (mutated in 40% of ccRCC) rescues VHL-induced replication stress, maintaining cellular fit

226 using ERK inhibitors, however, resensitizes VHL- and EglN3-deficient cells that are otherwise cispla

227 antly higher for hereditary cluster 1 (SDHx, VHL) tumors than for hereditary cluster 2 (RET, NF1) and

228 bevacizumab PET might offer a tool to select VHL patients for anti-VEGF therapy.

229 t transcription and tumor growth in selected VHL-deficient clear-cell renal cell carcinoma (ccRCC) mo

230 describe dTAG(V)-1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12(

231 offers a novel chemical probe for selective VHL knockdown, and demonstrates the potential for a new

232 Unexpectedly, some VHL-mutant ccRCCs were resistant to PT2399.

233 kidneys of nephron progenitor cell-specific VHL knockout mice begin to exhibit reduced maturation of

234 In addition, several type-specific VHL disease-causing mutants, including those that have r

235 in some individuals with seemingly sporadic VHL-related tumor types, as </= 10% of pheochromocytoma

236 rthermore, inhibition of cleavage stabilized VHL protein and thereby promoted HIF downregulation.

237 Daam2 promotes tumorigenesis by suppressing VHL expression.

238 m2 can bind directly to the tumor suppressor VHL, and conjugate nedd8 to VHL within a region that is

239 n of the von Hippel-Lindau tumor suppressor (VHL) protein in the forkhead box FOXD1 cell lineage, fro

240 encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases.

241 ncluding von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD

242 the most effective way to manage symptomatic VHL-HBs.

243 KI 1447 and GSK 429286, selectively targeted VHL-deficient CC-RCC.

244 eloping new therapeutic approaches targeting VHL deficiency in VHL diseases.

245 ment of therapeutic strategies for targeting VHL-deficient RCC.

246 apoptosis and growth inhibitory effect than VHL wild-type Caki-2 and ACHN RCC cell lines.

247 We conclude that VHL-HBs harbor multiple SSTR subtypes that offer actiona

248 Unexpectedly, we found that VHL promotes Th17 differentiation.

249 Here we report that VHL has an equally important function distinct from its

250 We report that VHL-deficient and VHL-positive renal cancer cells posses

251 d pharmacological approaches and showed that VHL was first cleaved at the N-terminus by chymotrypsin

252 Here we have shown that VHL-/- RCC cells rely on RC-derived aspartate to maintai

253 rough metabolic regulation, and suggest that VHL is required for normal kidney development.

254 tivation of STAT3 and SMAD2, suggesting that VHL indirectly or directly regulates these critical sign

255 The VHL gene product, pVHL, is the substrate recognition uni

256 inherited cancer, caused by mutations in the VHL gene, many of which render the VHL protein (pVHL) un

257 Alterations in the VHL tumor suppressor stabilizing the hypoxia-inducible f

258 f hypoxia-inducible factor (HIF) beta in the VHL-deficient CC-RCC had a protective effect against Y-2

259 on that resulted in increasing VEGF-A in the VHL-wt RCC cells.

260 different oxygen conditions may involve the VHL-impacted ubiquitination and nuclear localization of

261 Inactivation of the VHL (Von Hippel Lindau) tumour suppressor has long been

262 tein is the substrate binding subunit of the VHL E3 ubiquitin ligase, which targets hydroxylated alph

263 In ccRCC the biallelic inactivation of the VHL gene leads to stabilization of hypoxia-inducible fac

264 Inactivation of the VHL tumor suppressor gene is the signature initiating ev

265 are initiated by somatic inactivation of the VHL tumor suppressor gene.

266 the oncogenic transcriptional output of the VHL-HIF axis and provide a functional explanation for th

267 Activation of the VHL-HIF1a-VEGF-EPO pathway in the adult retina led to lo

268 xpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenoty

269 erent mechanism, that is the blockade of the VHL:HIF-alpha protein-protein interaction downstream of

270 ivating the development of inhibitors of the VHL:HIF-alpha protein-protein interaction.

271 udy provides new chemical tools to probe the VHL-HIF pathways and new VHL ligands for next-generation

272 ns in the VHL gene, many of which render the VHL protein (pVHL) unstable.

273 A KRAS-specific DARPin fused to the VHL E3 ligase is compared to a pan-RAS intracellular sin

274 ID2 binds to the VHL ubiquitin ligase complex, displaces VHL-associated C

275 hm (a tailored algorithm) developed by three VHL clinicians.

276 racellular expression of monobodies fused to VHL, an E3 ubiquitin ligase substrate receptor, results

277 ing different polyethylene glycol linkers to VHL ligand VH032.

278 tumor suppressor VHL, and conjugate nedd8 to VHL within a region that is important for the p53-VHL in

279 ceptibility genes (including 2 each in TP53, VHL, and BRCA1), 1 recessive liver disorder with hepatoc

280 rapidly degraded in cells lacking wild-type VHL or in which EglN3 was inactivated genetically or by

281 ise mechanisms of AR roles in VHL wild-type (VHL-wt) ccRCC, remain unclear.

282 Compared with wild-type, VHL-deficient Th17 cells had elevated glycolysis and gly

283 Surgically unresectable VHL-HBs or those in frail patients are challenging probl

284 IF-1alpha failed to undergo EMT changes upon VHL knockout.

285 We aimed to assess whether VHL manifestations can be visualized with (89)Zr-bevaciz

286 increased levels of TNFalpha associated with VHL loss forced VHL-deficient cells to rely on intact RI

287 lyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation.

288 We show that 4.1R associates with VHL and, when overexpressed, reverses myogenin ubiquitin

289 acroPROTAC-1 bound in a ternary complex with VHL and the second bromodomain of Brd4 validated the rat

290 iltrates: long-lived patients, enriched with VHL but depleted of BAP1 mutations, have high levels of

291 deletions of FTO are mutually exclusive with VHL loss in pan cancer datasets.

292 Here we found that AR interacted with VHL to modulate the metastasis of VHL-wt ccRCC via an ox

293 compounds that are synthetically lethal with VHL deficiency in CC-RCC.

294 ferentiation, we bred Six2-TGC(tg) mice with VHL(lox/lox) mice to generate mice with a conditional de

295 Materials and Methods Patients with VHL disease who underwent surgical resection of tumors b

296 ccRCC patients with VHL loss-of-function mutations displayed elevated SFMBT1

297 protocol (VNC; n = 149) in 747 patients with VHL syndrome in the National Institutes of Health Clinic

298 F2alpha-targeted therapies for patients with VHL-associated tumors.

299 cs professionals who encounter patients with VHL.

300 ages with high affinity and specificity with VHL as its only major cellular target, leading to select

301 renal cancer cells (ccRCC), with or without VHL, upon the deprivation of individual amino acids.