ライフサイエンスコーパス: tuberin

1 lex (TSC) genes TSC1 (hamartin) and/or TSC2 (tuberin).

2 he tuberous sclerosis complex 2 gene product tuberin.

3 via Rheb is an mTOR-independent function of tuberin.

4 t the evolutionarily conserved C terminus of tuberin.

5 codes for hamartin, or TSC2, which codes for tuberin.

6 ntaining the RING zinc finger motif binds to tuberin.

7 apping 14-3-3 and Akt recognition site(s) in tuberin.

8 he interaction between endogenous 14-3-3 and tuberin.

9 uct of the tuberous sclerosis-2 (TSC2) gene, tuberin.

10 t was not important for the interaction with tuberin.

11 growth suppressing functions of hamartin and tuberin.

12 6, the X-linked retinoschisis gene and TSC2/tuberin.

13 is likely dependent on its interaction with tuberin.

14 and analyze pathological point mutations in tuberin.

15 xpression, paralleling its effect on Akt and tuberin.

16 he tuberous sclerosis complex 2 gene product tuberin.

17 ange in phosphorylation of either Akt/PKB or tuberin.

18 alized within the carboxyl 73 amino acids of tuberin.

19 Phosphorylation of Akt and tuberin, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) l

20 findings demonstrate for the first time that tuberin activates Rho and regulates cell adhesion and mi

21 AMPK and tuberin activation prevent tubulointerstitial injury ind

22 Tuberin also coimmunoprecipitated with 14-3-3, confirmin

23 Hamartin (amino acids 302-430) and tuberin (amino acids 1-418) interacted strongly with one

24 of either TSC genes (TSC1, hamartin or TSC2, tuberin), an event that is implicated in the induction o

25 milar decrease in the activation of AMPK and tuberin and activation of mTOR with increase in Nox4 and

26 vated Ras also induce the phosphorylation of tuberin and collaborates with the nutrient-sensing pathw

27 ose leads to phosphorylation/inactivation of tuberin and downregulation of OGG1 via a redox-dependent

28 a protein expression through inactivation of tuberin and downstream activation of ribosomal protein S

29 Tuberin and E6TP1 protein levels are tightly regulated t

30 An in vivo association between full-length tuberin and ERalpha was observed in HEK 293 cells and EL

31 trast, poor association was observed between tuberin and ERbeta.

32 ant increases in the basal levels of phospho-tuberin and fibronectin expression in the kidney cortex.

33 forms of multiple Akt substrates, including tuberin and FOXO proteins.

34 Tuberin and hamartin form a complex that inhibits signal

35 Tuberin and Hamartin form a tumor suppressor heterodimer

36 Tuberin and hamartin function together as a complex in m

37 In cortical neurons, Pam co-localizes with tuberin and hamartin in neurites and growth cones.

38 Tuberin and hamartin inhibit signaling by the mammalian

39 es that underlie tuberous sclerosis complex, tuberin and hamartin, lie at the center of an important

40 erin complexes, promoting phosphorylation of tuberin and increased degradation of hamartin-tuberin co

41 PTE cells to HG increased phosphorylation of tuberin and p70S6K, phosphorylation of Bcl-2, expression

42 ated with mitogen-induced phosphorylation of tuberin and recognition of tuberin by an alpha-Akt phosp

43 conclusion that REDD1 functions upstream of Tuberin and Rheb to down-regulate mTOR signaling in resp

44 ox) inhibit Akt-dependent phosphorylation of tuberin and stabilizes tuberin protein levels in VHL-def

45 e results suggested that hamartin stabilizes tuberin and this contributes to the inhibition of cell g

46 he tumor suppressor TSC1 (hamartin) or TSC2 (tuberin) and increased angiogenesis, fibrosis, and abund

47 rotein kinase (AMPK) activation, inactivates tuberin, and activates mTOR.

48 t the cytoplasmic tail of PC1 interacts with tuberin, and the mTOR pathway is inappropriately activat

49 ta, epsilon, tau, eta, and sigma) could bind tuberin, and this interaction was abrogated by competiti

50 on of TSC1 increased the endogenous level of tuberin, and transient co-transfection of TSC1 with TSC2

51 man NTera2 neurons (NT2N) transfected with a tuberin antisense construct that reduced tuberin express

52 e cell proliferative effects of hamartin and tuberin are partly mediated through beta-catenin.

53 We also show that S939 and T1462 of tuberin are PI3K-regulated phosphorylation sites and tha

54 Hamartin and tuberin are products of the tumor suppressor genes, TSC1

55 ither of two genes, TSC1 (hamartin) or TSC2 (tuberin), are responsible for most cases.

56 r functions of TSC2 and its protein product, tuberin, are not known, somatic mutations in the TSC2 tu

57 These data identify tuberin as a determinant of polycystin-1 functional loca

58 e tuberous sclerosis complex-2 gene product, tuberin, as a potential target of Akt/PKB.

59 Increased levels of phosphorylated tuberin associated with an increase in fibronectin expre

60 was found to interact with and phosphorylate tuberin at a regulatory site, Ser-1798, located at the e

61 omozygous for the del3 allele express mutant tuberin at low levels, and show enhanced activation of m

62 Phosphorylation of tuberin at serines 939 and 981 does not alter its intrin

63 C/MAPK signaling leads to phosphorylation of tuberin at sites that overlap with and are distinct from

64 hamartin colocalizes with hypophosphorylated tuberin at the membrane, where tuberin exerts its GTPase

65 reflected by differential phosphorylation of tuberin at threonine 1462 and serine 1798, respectively,

66 These results demonstrate that tuberin binds specifically to ERalpha and inhibits E2-in

67 Third, hamartin and tuberin blocked the ability of amino acids to activate S

68 Thus, tuberin bound by 14-3-3 in response to AKT phosphorylati

69 Ectopic expression of hamartin and wild-type tuberin, but not mutant tuberin, reduced beta-catenin st

70 as repressed by coexpression of hamartin and tuberin, but the activity of rapamycin-resistant mutants

71 and inactivation of the TSC2-encoded protein tuberin by AKT.

72 TOR signaling by means of phosphorylation of tuberin by Akt.

73 Recognition of tuberin by an alpha-14-3-3 binding site-specific antibod

74 hosphorylation of tuberin and recognition of tuberin by an alpha-Akt phosphorylation substrate antibo

75 Recognition of tuberin by both antibodies was blocked by inhibiting pho

76 tial competitive relationship for binding of tuberin by ERalpha and CaM.

77 Phosphorylation of tuberin by phorbol 12-myristate 13-acetate was reduced b

78 substrate of Akt and that phosphorylation of tuberin by PI3K/Akt is a major mechanism controlling ham

79 Phosphorylation of tuberin, by Akt, results in its inactivation.

80 nslational inactivation of the TSC2 protein, tuberin, by physiologically inappropriate phosphorylatio

81 mutations in the extreme carboxy-terminus of tuberin can result in LAM.

82 Expression of this mutant tuberin caused a marked reduction in TSC1-TSC2 interacti

83 t phosphorylated hamartin and phosphorylated tuberin co-immunoprecipitate with the mitotic kinase Plk

84 Indeed, hamartin and tuberin co-immunoprecipitated with glycogen synthase kin

85 In cultured cortical neurons, hamartin and tuberin co-localize with neurofilament light chain prefe

86 a novel interaction partner for the hamartin/tuberin complex and implicate hamartin and mTOR in the r

87 artin regulates the function of the hamartin-tuberin complex during the G2/M phase of the cell cycle.

88 However, the regulation of the hamartin-tuberin complex in the context of the physiologic role a

89 n and it is possible to recover the hamartin-tuberin complex over the neurofilament light chain rod d

90 or some of the CNS functions of the hamartin-tuberin complex, and abolishing this through mutations i

91 ively regulates the activity of the hamartin/tuberin complex.

92 e inhibition of p70S6 kinase by the hamartin-tuberin complex.

93 strate that Akt/PKB associates with hamartin-tuberin complexes, promoting phosphorylation of tuberin

94 uberin and increased degradation of hamartin-tuberin complexes.

95 ddress these issues a series of hamartin and tuberin constructs were used to assay for interaction in

96 Tuberin contains a RapGAP homology domain responsible fo

97 Importantly, we found that tuberin contributed to the protective effects of AMPK an

98 esize that Pam, through its interaction with tuberin, could regulate the ubiquitination and proteasom

99 Short interfering RNA down-regulation of tuberin decreased the p42/44 MAPK phosphorylation and B-

100 associated with enhanced phosphorylation of tuberin, decreased OGG1 protein expression, and 8-oxodG

101 mass was significantly greater in partially tuberin-deficient (TSC2(+/-) ) diabetic rats than wild-t

102 In tuberin-deficient cells, intracellular trafficking of po

103 In contrast, in tuberin-deficient ELT-3 cells (TSC2-/-), PDGF stimulatio

104 ic protein synthesis via PTEN, hamartin, and tuberin degradation.

105 , we expressed a dominant negative allele of tuberin (DeltaRG) behind the cytomegalovirus promoter in

106 ollowing TGF-beta1 stimulation that requires tuberin-dependent activity.

107 s reduced in the presence of Wnt whereas the tuberin-Dishevelled interaction was increased.

108 mbryos lacking functional Tsc2 gene product, tuberin, displayed dysraphia and papillary overgrowth of

109 the neuroepithelium, indicating that loss of tuberin disrupted the normal development of this tissue.

110 whereby the inactivating phosphorylation of tuberin downstream of phosphatidylinositol (PI) 3-kinase

111 Critical functions of hamartin and tuberin, encoded by the TSC1 and TSC2 genes, are likely

112 Normal cellular functions of hamartin and tuberin, encoded by the TSC1 and TSC2 tumor suppressor g

113 A region of tuberin encoding a putative coiled-coil (amino acids 346

114 ort the hypothesis that interactions between tuberin, ERalpha, and CaM may play a critical role in th

115 Additionally, tuberin-ERalpha interactions were found to be modulated

116 hosphorylated tuberin at the membrane, where tuberin exerts its GTPase-activating protein (GAP) activ

117 Tuberin interacts with phosphohamartin, and tuberin expression attenuates the phosphorylation of exo

118 Inhibition of tuberin expression by Tsc2 antisense greatly reduces the

119 Also, inhibition of tuberin expression during stimulation of monocytic diffe

120 We examined the effect of tuberin expression in ELT-3 smooth muscle cells on the g

121 Tuberin expression increased cell adhesion in both cell

122 We found that tuberin expression increases p42/44 MAPK phosphorylation

123 Tuberin expression was limited to the brain.

124 ELT3 cells lack endogenous tuberin expression.

125 h a tuberin antisense construct that reduced tuberin expression.

126 Hamartin and tuberin form a heterodimer that functions as a major cel

127 Hamartin and tuberin form a heterodimer that inhibits the mammalian t

128 The gene products hamartin and tuberin form the TSC complex that acts as GTPase-activat

129 Interaction of hamartin with tuberin forms a heterodimer that inhibits signaling by t

130 in the protein levels of the Akt substrates tuberin, FOXO1, and FOXO3a.

131 A mutant of tuberin from a patient missense mutation of TSC2 was als

132 erexpression of Rheb, a downstream target of Tuberin function and a positive upstream effector of mTO

133 by Disheveled, suggesting that hamartin and tuberin function at the level of the beta-catenin degrad

134 ssion of MCP-1 seems to be caused by loss of tuberin function because Eker rat embryonic fibroblasts

135 Here, we show that hamartin and tuberin function together to inhibit mammalian target of

136 kt is a major mechanism controlling hamartin-tuberin function.

137 eb-mediated S6K1 activation, suggesting that Tuberin functions as a Rheb GTPase activating protein (G

138 genetic evidence for individual hamartin and tuberin functions that may explain some of the genotype-

139 hamartin (N198_F199delinsI;593-595delACT) or tuberin (G294E and I365del), abolished or dramatically r

140 Supporting this notion, TSC patient-derived Tuberin GAP domain mutants were unable to inactivate Rhe

141 s in either the TSC1 (hamartin) or the TSC2 (tuberin) gene.

142 of each and every interacting partner of the tuberin-hamartin complex could potentially alter the dis

143 identified as an interactor of Myc, with the tuberin-hamartin complex in the brain.

144 itination and proteasomal degradation of the tuberin-hamartin complex particularly in the CNS.

145 TOR with mTOR, and increased assembly of the tuberin-hamartin complex.

146 Overexpression of the Tuberin-Hamartin heterodimer inhibits Rheb-mediated S6K1

147 Here we show that tuberin-hamartin heterodimers block protein kinase C (PK

148 ar binding partner hamartin, suggesting that tuberin-hamartin interactions negatively impact the abil

149 These findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibito

150 uced assembly of the mTOR regulatory complex Tuberin.Hamartin is disrupted in L6 myoblasts following

151 nhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mTOR si

152 Indeed, hamartin and tuberin have been shown to interact stably in vitro and

153 We found that TS model cells derived from tuberin heterozygous mice and from a human renal angiomy

154 f diabetes also increased phosphorylation of tuberin in association with mTOR activation (measured by

155 We found that expression of human tuberin in both MDCK and ELT3 cells was associated with

156 beta and ERK-1/-2 suggest a pivotal role for tuberin in directing the signaling events that dictate t

157 lel with this observation, the expression of tuberin in ELT-3 cells also resulted in significant inhi

158 In contrast, the expression of tuberin in ELT-3 smooth muscle cells resulted in signifi

159 Here we report a critical role for tuberin in late stage myeloid cell differentiation.

160 a target of the GTPase-activating domain of tuberin in mammalian cells and in Drosophila.

161 Thus, expression of a dominant negative tuberin in multiple tissues can lead to a tissue-specifi

162 Akt phosphorylation sites were identified in tuberin in silico.

163 In addition, forced expression of tuberin in tuberin-null cells abolished the expression o

164 e Rho, we stably expressed full-length human tuberin in two cell types: MDCK cells and ELT3 cells.

165 Moreover, Akt/PKB can phosphorylate tuberin in vitro and in vivo.

166 and subsequent tuberous sclerosis complex 2/tuberin inactivation or by suppression of AMP-activated

167 patient-derived cell line (bearing biallelic Tuberin inactivation), we demonstrate that E2 stimulates

168 he target of the GTPase-activating domain of tuberin, inhibited wild-type B-Raf kinase but not activa

169 As overexpression of tuberin inhibits cell growth, and hamartin is known to b

170 es, one of which (Thr417) is in the hamartin-tuberin interaction domain.

171 emonstrate that the amino-terminal region of tuberin interacts specifically with the MH2 domain of SM

172 Tuberin interacts with phosphohamartin, and tuberin expr

173 Re-introduction of wild type tuberin into LAMD-SM, ELT3, and ERC15 cells abolished ph

174 Our results indicate that tuberin is a direct physiological substrate of Akt and t

175 p22(phox)-mediated inactivation of tuberin is associated with an increase in ribosomal prot

176 independent studies have shown that loss of tuberin is associated with elevated AMPK signaling and a

177 ylation, and 3) defective phosphorylation of tuberin is associated with loss of its tumor suppressor

178 mals, suggest that the loss or inhibition of tuberin is associated with up-regulation of cyclin D1.

179 bilization was explained by the finding that tuberin is highly ubiquitinated in cells, while the frac

180 In this study, we showed that tuberin is phosphorylated at serine and tyrosine residue

181 Our data show for the first time that 1) tuberin is phosphorylated at tyrosine and serine residue

182 In response to growth signals, tuberin is phosphorylated by AKT and translocates to the

183 Upon insulin or growth factor stimulation, tuberin is phosphorylated by several kinases, including

184 e demonstrate that, upon activation of PI3K, tuberin is phosphorylated on consensus recognition sites

185 At the cellular level, tuberin is required as a critical regulator of cell grow

186 coding 37 amino acids near the N terminus of tuberin, is deleted.

187 In addition, the gene product of TSC2, tuberin, is necessary for normal function of the polycys

188 TSC2, or tuberin, is the product of the tuberous sclerosis tumor

189 However, in cells expressing tuberin, it is not known how repression of mTOR signalin

190 rtin but has a deletion in the C terminus of tuberin, leading to constitutive activation of rap1 and

191 fection of TSC1 with TSC2 resulted in higher tuberin levels.

192 The tumor suppressor effect of tuberin lies in its GTPase-activating protein activity t

193 Akt also inhibits tuberin-mediated degradation of p27(kip1), thereby promo

194 expression in GCs reflects loss of hamartin-tuberin-mediated mTOR pathway inhibition.

195 tuberin occurs at the C-terminal end of the tuberin molecule.

196 locus mutations were confirmed and the mean tuberin mRNA expression levels was reduced across all ni

197 Tuberin mRNA levels were reduced in GCs from TSC patient

198 nnin-sensitive sequential phosphorylation of tuberin, mTOR, p70S6 kinase (p70S6K), and 4E-BP1.

199 Because the tuberin/mTOR pathway can modulate apoptosis, we studied

200 These data show that the tuberin/mTOR pathway promotes apoptosis of tubular epith

201 Finally, we find that a tuberin mutant lacking the major PI3K-dependent phosphor

202 ermophilum and a homology model of the human tuberin N terminus are presented.

203 tment rapidly reduced levels of hamartin and tuberin, negative regulators of mTOR, in a calpain-depen

204 Our data suggest that hamartin and tuberin negatively regulate beta-catenin stability and a

205 These data demonstrate that tuberin negatively regulates the activity of S6 and p70S

206 tive and rapamycin-insensitive mechanisms of tuberin-null cell growth, likely via Rheb and Rho inhibi

207 In addition, forced expression of tuberin in tuberin-null cells abolished the expression of fibronect

208 lung colonization of intravenously injected tuberin-null cells by 3-fold, which is blocked by treatm

209 e of women associated with the metastasis of tuberin-null cells with hyperactive mammalian target of

210 metastasis via enhanced survival of detached tuberin-null cells.

211 In vitro, E(2) inhibits anoikis of tuberin-null cells.

212 The growth-promoting effect of E2 in tuberin-null ELT-3 smooth muscle cells was ERalpha-speci

213 e in circulating tumor cells in mice bearing tuberin-null xenograft tumors.

214 indicating that binding between ERalpha and tuberin occurs at the C-terminal end of the tuberin mole

215 Furthermore, the opposing effects of tuberin on estrogen-induced activation of PDGFRbeta and

216 e 3-kinase (PI3K)/Akt pathway phosphorylates tuberin on Ser-939 and Thr-1462 that inhibits the tumor

217 strated that SGK1 induces phosphorylation of tuberin, p70s6kinase, and GSK3beta in CMs, which may con

218 nt as downstream effects of the hamartin and tuberin pathway in TSC.

219 Using a protein domain microarray, a tuberin peptide containing Ser(939) demonstrated phospho

220 phorylated but not unphosphorylated Ser(939) tuberin peptide.

221 omoted cell injury by blocking AMPK-mediated tuberin phosphorylation and activation.

222 Hydrogen peroxide stimulates Akt and tuberin phosphorylation and decreases OGG1 protein expre

223 t significantly reduced high glucose-induced tuberin phosphorylation and restored OGG1 expression.

224 ed ROS generation, Akt/protein kinase B, and tuberin phosphorylation and resulted in deceased 8-oxodG

225 dependent and -dependent mechanisms modulate tuberin phosphorylation in vivo.

226 ificant decrease in AMPK phosphorylation and tuberin phosphorylation on its AMPK-dependent activating

227 ated TSC2 mutation (Y1571H) nearly abolished tuberin phosphorylation when stimulated with pervanadate

228 es, 2) TSC1-TSC2 interaction is regulated by tuberin phosphorylation, and 3) defective phosphorylatio

229 nal cell carcinoma correlates with increased tuberin phosphorylation, decreased tuberin protein level

230 Inhibition of mTOR had no effect on AMPK or tuberin phosphorylation, indicating that mTOR is downstr

231 active Akt, including Akt1 and Akt2, induces tuberin phosphorylation.

232 that correlates with the increase in Akt and tuberin phosphorylation.

233 Taken together, these data suggest that tuberin plays a central role in the development of renal

234 nt phosphorylation of tuberin and stabilizes tuberin protein levels in VHL-deficient renal carcinoma

235 increased tuberin phosphorylation, decreased tuberin protein levels, and increased phosphorylation of

236 ree non-pathogenic missense polymorphisms of tuberin (R261W, M286V, R367Q) in the same region as the

237 ared to wild type cells, and was reversed by tuberin re-expression in Tsc2-/- MEFs.

238 , no change in endocytosis was observed upon tuberin re-expression in Tsc2-/- MEFs.

239 martin and wild-type tuberin, but not mutant tuberin, reduced beta-catenin steady-state levels and it

240 In this study, we show that tuberin regulates the localization of E-cadherin via an

241 First, coexpression of hamartin and tuberin repressed phosphorylation of 4E-BP1, resulting i

242 , TSC1 and TSC2, which code for hamartin and tuberin respectively, play central roles in regulating c

243 TSC1 and TSC2 (also known as hamartin and tuberin, respectively) form a functional complex and neg

244 teins encoded by TSC1 and TSC2, hamartin and tuberin, respectively, associate with each other forming

245 Their protein products, hamartin and tuberin, respectively, form a functional complex that af

246 of TSC1 and TSC2, also known as hamartin and tuberin, respectively, form a physical and functional co

247 and TSC2 proteins, also called hamartin and tuberin, respectively, have been shown to regulate cell

248 cts of the TSC1 and TSC2 genes, hamartin and tuberin, respectively, heterodimerize and inhibit the ma

249 SC1 or TSC2 genes, which encode hamartin and tuberin, respectively.

250 enes TSC1 or TSC2, which encode hamartin and tuberin, respectively.

251 ither TSC1 or TSC2, which encode Hamartin or Tuberin, respectively.

252 nes, TSC1 and TSC2, that encode hamartin and tuberin, respectively.

253 ich encode the protein products hamartin and tuberin, respectively.

254 lerosis complex 2 (TSC2) gene, which encodes tuberin, result in the development of TSC and lymphangio

255 f-BRAF-driven NSC proliferation results from tuberin/Rheb-mediated mammalian target of rapamycin (mTO

256 the identification of Rheb as the target of tuberin's (TSC2) GTPase activating protein (GAP) domain.

257 e-activating protein Tuberin, which inhibits Tuberin's ability to inactivate the small GTPase Rheb.

258 wo observations fostered the hypothesis that tuberin's impact on estrogen-mediated signaling might be

259 ere found to be modulated by the presence of tuberin's predominant intracellular binding partner hama

260 Co-expression of tuberin stabilized hamartin, which is weakly ubiquitinat

261 Tuberin strongly augments transforming growth factor (TG

262 However, the regions of hamartin and tuberin that interact have not been well defined, and th

263 biquitinated in cells, while the fraction of tuberin that is bound to hamartin is not ubiquitinated.

264 Tuberin, the product of the tuberous sclerosis complex 2

265 Loss of tuberin, the product of TSC2 gene, increases mammalian t

266 Hamartin and tuberin, the products of the TSC1 and TSC2 genes, respec

267 Hamartin and tuberin, the products of TSC1 and TSC2, respectively, fo

268 We hypothesized that tuberin, the protein product of TSC2, binds to estrogen

269 Tuberin, the Tsc2 gene product, integrates the phosphati

270 To determine whether tuberin, the TSC2 product, can also activate Rho, we sta

271 On growth factor stimulation, tuberin, the TSC2 protein, is phosphorylated by Akt, the

272 s cell growth, and hamartin is known to bind tuberin, these results suggested that hamartin stabilize

273 dent on Wnt stimulation such that binding of tuberin to GSK3 and Axin was reduced in the presence of

274 3K pathways converge on the tumor suppressor tuberin to inhibit its function.

275 nteractions negatively impact the ability of tuberin to modulate ERalpha-mediated gene transcription

276 nsic GAP activity toward Rheb but partitions tuberin to the cytosol, where it is bound by 14-3-3 prot

277 enhanced in cells lacking expression of the tuberin (TSC2(-/-)) or hamartin (TSC1(-/-)) genes, consi

278 SC2, whose gene products hamartin (TSC1) and tuberin (TSC2) constitute a putative tumor suppressor co

279 Tuberin (TSC2) is a tumor suppressor gene.

280 Tuberin (TSC2) was weak or absent in angiomyolipomas, bu

281 its inhibitor, the GTPase-activating protein tuberin (TSC2), may play a role in this pathway.

282 ase primarily affecting young women in which tuberin (TSC2)-null cells metastasize to the lungs.

283 reatment alone in inhibiting the survival of tuberin (TSC2)-null cells, growth of TSC2-null xenograft

284 by loss or malfunction of hamartin (tsc1) or tuberin (tsc2).

285 rtin (TSC1) and loss of immunoreactivity for tuberin (TSC2).

286 e cells, we show that ELT-3 cells expressing tuberin (TSC2+/+) respond to platelet-derived growth fac

287 a binding site for the tumor suppressor gene tuberin (tuberous sclerosis complex-2).

288 ation with ERalpha and the C-terminal end of tuberin was also observed in vivo and in vitro, indicati

289 eover, except for a subset of kidney tumors, tuberin was expressed in both human and mouse tumors.

290 The amino-terminal two-thirds of tuberin was responsible for its ubiquitination and for s

291 In the study presented here, tuberin was shown to co-immunoprecipitate and directly b

292 y curtailed the growth inhibitory effects of tuberin when overexpressed in COS1 cells, consistent wit

293 Moreover, in vitro studies reveal that Tuberin, when associated with Hamartin, acts as a Rheb G

294 Together, our data suggest that loss of tuberin, which causes mTOR activation, leads to a novel

295 is complex 2 (TSC2) gene encodes the protein tuberin, which functions as a key negative regulator of

296 phorylation of the GTPase-activating protein Tuberin, which inhibits Tuberin's ability to inactivate

297 factor (IGF) 1 stimulates phosphorylation of tuberin, which is inhibited by the phosphatidylinositol

298 tigated the effect of the signaling molecule tuberin, which modulates the mammalian target of rapamyc

299 hamartin interacts with Plk1 independent of tuberin with all three proteins present in a complex.

300 ide the first structural information on TSC2/tuberin with novel insight into the molecular function.

301 Furthermore, gene silencing of tuberin with siRNA decreased cleavage of PARP.