ライフサイエンスコーパス: Rheb

1 conserved (e.g. Rap) or not catalytic (e.g. Rheb).

2 t inhibits its ability to bind and sequester Rheb.

3 action with its target small GTPase protein, Rheb.

4 mediated by 14-3-3 interaction with Tctp and Rheb.

5 3 proteins physically interact with Tctp and Rheb.

6 rface, where it interacts with its activator Rheb.

7 1 and mediated by the miR-155 target protein Rheb.

8 mino acids, Rag GTPases, growth factors, and Rheb.

9 ator of the myogenic functions of raptor and Rheb.

10 ORC1) that was dependent on the small GTPase Rheb.

11 partment that contains the mTORC1 activator, Rheb.

12 osis of patients with cancers overexpressing RHEB.

13 t FTS inhibits mTOR at a level downstream of Rheb.

14 rin's ability to inactivate the small GTPase Rheb.

15 at is devoid of FKBP38 is still activated by Rheb.

16 lly increased by the addition of recombinant Rheb.

17 by impairing the interaction of Raptor with Rheb.

18 ating protein (GAP) towards the small GTPase Rheb.

19 abling activation of mTOR by the Ras homolog Rheb.

20 This binding induces the transactivation of Rheb.

21 tly tagged endogenous Caenorhabditis elegans RHEB-1 and DAF-15/Raptor are expressed ubiquitously and

22 We observed that deletion of RHEB-1 similarly conferred L3 arrest.

23 of its target Ras homolog enriched in brain (Rheb), a critical activator of mTOR signaling.

24 gested that Ras homologue enriched in brain (Rheb), a direct activator of mTOR, and its inhibitor, th

25 have no impact on the signals that regulate Rheb, a GTPase required for the activation of mTOR compl

26 lexes with the ubiquitin-E3-ligase Siah1 and Rheb, a small G protein that activates mTOR.

27 of the TOR (target of rapamycin) complex via Rheb, a small GTPase.

28 Genetic suppression of RAPTOR or RHEB ablated P-S6 and restored sensitivity to the tyrosi

29 FKBP38, a recently proposed mediator of Rheb action, appears not to be involved in the Rheb-depe

30 aortic constriction and exercise upregulated RHEB, activated mTORC1, and induced cardiac hypertrophy

31 In this study, we demonstrate that Rheb activates AMPK and reduces p27 levels in Tsc2-null

32 In summary, overexpression of Rheb activates mTOR signaling via a PI3K/PKB-independent

33 RC1 signaling, which rather is determined by Rheb activation of mTOR catalytic activity, through mech

34 anism of TORC2 activation that is similar to Rheb activation of TOR complex 1.

35 ed that precancerous cells with constitutive Rheb activation through loss of tuberous sclerosis compl

36 stress, thereby reducing CM death induced by Rheb activation.

37 High Rheb activity in TSC mutant cells inhibits aggresome for

38 Consequently, when Rheb activity increases, cells become more resistant to

39 RagC and RagD GTPases, but is insensitive to RHEB activity induced by growth factors.

40 Knockdown of FOG2, p110alpha, and RHEB ameliorated invasive and metastatic propensities of

41 , we identify Ras homolog enriched in brain (Rheb), an activator of mTOR, as a novel protein substrat

42 -TBC1D7 complex (the TSC complex) to turn on Rheb, an essential activator of mTORC1.

43 nhibitory action of FKBP38 is antagonized by Rheb, an oncogenic small GTPase, which interacts with FK

44 nstitutively active form of the small GTPase Rheb, an upstream activator of mTor.

45 activates ER stress and ATF6, which induces RHEB and activates mTORC1.

46 factor-responsive pathway mediated via TSC2/Rheb and an amino acid-responsive pathway mediated via t

47 otein 3 (BNIP3)-a negative regulator of both Rheb and Bcl2 prosurvival family members-as a key downst

48 ation of mTOR with positive regulators (i.e. Rheb and eIF3F) is consistent with an enhanced mRNA tran

49 xercise led to the dissociation of TSC2 from Rheb and increased in the co-localisation of mTOR and Rh

50 In the presence of Rheb and insulin, PRAS40 release is abolished by Akt inh

51 skeletal muscle-specific knock-out mice for Rheb and iTSC2KO mice.

52 erodimer is a critical negative regulator of Rheb and mTOR activation.

53 equent study indicated an increased level of Rheb and mTOR expression in HCV-infected hepatocytes.

54 Rheb and mTORC1 may represent therapeutic targets to red

55 e lysosomal surface, where subpopulations of Rheb and mTORC1 reside.

56 exhibited deregulated cardiac activation of Rheb and mTORC1, particularly during ischemia.

57 x that acts as GTPase-activating protein for Rheb and negatively regulates the mammalian target of ra

58 nd Notch pathways, driven by the delivery of Rheb and Notch1 esRNA, in AML cells depleted of Rheb tha

59 molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 c

60 that C. elegans expresses orthologs for the Rheb and RalA/B GTPases and for RalGAPalpha/beta, but no

61 atively regulates the activity of the GTPase Rheb and thereby inhibits mammalian target of rapamycin

62 sults not only establish a critical role for Rheb and TSC2 in the mechanical activation of mTOR signa

63 ag heterodimer on the lysosome accumulate Ub-Rheb, and blockade of its degradation instigates robust

64 and Ras family GTPases such as Cdc42, RhoA, Rheb, and N-Ras, and can identify GEFs by use of GDP-bou

65 with TOR signaling components including TOR, Rheb, and S6K.

66 In contrast, mTORC1 regulators Raptor and Rheb are dispensable for NKT17 differentiation, despite

67 The hypertrophic effects of Rheb are driven through a rapamycin-sensitive (RS) mecha

68 Altogether, our study defines Rheb as a novel physiological regulator of BACE1 levels

69 We report the mTOR activator gene RHEB as an ID gene that is associated with megalencephal

70 ORC1 through the combined effects of TSC and RHEB as part of a multiprotein complex localized on lyso

71 recruitment of mTORC1 and the TSC complex to Rheb at the lysosomal surface serve to integrate diverse

72 f BACE1 levels and Abeta generation, and the Rheb-BACE1 circuitry may have a role in brain biology an

73 The activation of mTORC1 is specific to Rheb, because other G-proteins such as KRas, RalA/B, and

74 RHEB binds to mTOR distally from the kinase active site,

75 mall GTPase Ras homologue enriched in brain (RHEB) binds and activates the key metabolic regulator mT

76 ox-sensitive regulation of mTORC1 occurs via Rheb but not the Rag small GTPase.

77 ruitment of Ras homologue enriched in brain (Rheb) but not mammalian target of rapamycin (mTOR) to en

78 ology domain responsible for inactivation of Rheb, but functions of other protein domains remain elus

79 TORC1 is controlled by the small GTPase Rheb, but little is known about TORC2 regulators.

80 of AMPK classically inhibits mTORC1 via TSC/RHEB, but several lines of evidence suggest additional m

81 , arginine relieves allosteric inhibition of Rheb by TSC.

82 res that significantly increased with higher Rheb(CA) concentrations.

83 We found that Rheb(CA) expression induced mTORC1 hyperactivation and i

84 (CA) mice, whereas the intermediate and high Rheb(CA) mice displayed spontaneous, recurrent seizures

85 No seizures were detected in the low Rheb(CA) mice, whereas the intermediate and high Rheb(CA

86 tively active Ras-homolog enriched in brain (Rheb(CA)) into subventricular zone NPCs increased mTOR a

87 Constitutively active Rheb (Rheb(CA)), the canonical activator of mTOR complex 1 (mT

88 At >19 dpe, newborn Rheb(CA)-expressing neurons displayed altered distributi

89 was notably higher in the regions containing Rheb(CA)-expressing neurons.

90 The activation of mTORC1 by Rheb can be faithfully reproduced in vitro by using mTOR

91 g a constitutively active form of the GTPase Rheb (caRheb) in adult neurons after a complete SCI in r

92 By interfering with TSC-Rheb complex, arginine relieves allosteric inhibition of

93 ds that decrease glutathione normalize GAPDH-Rheb complexes and mTOR activity in S47 cells.

94 Furthermore, Tsc2 deficiency and hyperactive Rheb constitutively activated mTOR and inhibited ephrin-

95 study, we investigated the possibility that Rheb controls apoptosis by regulating the interaction of

96 Taken together, our data suggest that Rheb controls proliferation of TSC2-deficient cells by a

97 es are consistently dephosphorylated in both Rheb-deficient CD4(+) T cells and T cells treated with r

98 By analyzing activated murine wild-type and Rheb-deficient CD4(+) T cells, as well as murine CD4(+)

99 However, these RHEB-deficient memory-like T cells failed to generate re

100 Rheb-deficient T cells failed to generate T(H)1 and T(H)

101 eb action, appears not to be involved in the Rheb-dependent activation of mTORC1 in vitro, because th

102 SC complex associates with the lysosome in a Rheb-dependent manner, and its dissociation in response

103 nonselective, membrane interactions support Rheb-dependent mTORC1 activation without the need for a

104 erminal CaaX motif on Rheb was essential for Rheb-dependent mTORC1 activation.

105 Importantly, we found that the Rheb-dependent release of Bcl-X(L) from FKBP38 facilitat

106 Furthermore, increased p27 levels following Rheb depletion correlated with reduced Cdk2 activity and

107 Mechanistically, we identified ATXN3 as a Ub-Rheb deubiquitinase whose lysosomal localization is bloc

108 we show that mTOR and its positive regulator Rheb display increased association in S47 cells; this is

109 forms abolishes the binding between Tctp and Rheb, disrupting organ development.

110 Active Rheb disrupts the interaction between dynein and misfold

111 Rheb does not induce autophosphorylation of mTOR.

112 f Tsc1 and overexpression of the Ras homolog Rheb each resulted in duplication of the bristle and soc

113 Expression of a constitutively active Rheb enhanced mTOR activity and increased the fiber size

114 xpected, the knockdown of raptor, as well as Rheb, enhances differentiation.

115 omal delivery of exosomal shuttle Notch1 and Rheb esRNA and component of gamma-secretase complex pres

116 Although farnesylated Rheb exhibited partial endoplasmic reticulum (ER) locali

117 This leads to Rheb expression and potentiates mTOR signaling to drive

118 nction in epithelial malignancy, we targeted Rheb expression to murine basal keratinocytes of transge

119 rowth, all of which were restored by ectopic RHEB expression.

120 Our findings offer direct evidence that RHEB facilitates multistage carcinogenesis through induc

121 CD4(+) T cells lacking the mTORC1 activator Rheb fail to secrete IFN-gamma under Th1 polarizing cond

122 ue to loss of RAS homolog enriched in brain (RHEB) failed to differentiate into effector cells but re

123 ) mutant prevented small GTP-binding protein Rheb from enhancing the phosphorylation of S6 kinase (S6

124 nd independent of Rag and Ragulator, but not Rheb, function.

125 In many eukaryotes, the small GTPase Rheb functions as a switch to toggle activity of TOR com

126 Rheb G63A stimulated phosphorylation of the mTORC1 subst

127 iation of TSC1 and TSC2 leading to decreased Rheb-GAP activity, without effects on the localization o

128 fic cellular growth conditions and possesses Rheb-GAP activity.

129 Substitution of Rheb Gly-63 with alanine impaired both intrinsic and TSC

130 th cysteine oxidants significantly increases Rheb GTP levels.

131 cells where the perinuclear localization of Rheb-GTP and mTOR coincided with the perinuclear assembl

132 colocalization of mTORC1 with its activator Rheb-GTP in a perinuclear region, thereby inducing 4E-BP

133 y increasing PI3K/Akt-mediated activation of Rheb-GTP via TSC2 suppression.

134 d manner and promote mTORC1 interaction with Rheb-GTP, the immediate activator.

135 anner through the colocalization of mTOR and Rheb-GTP, which occurs in association with the formation

136 no acid-dependent steps couple Rag-mTORC1 to Rheb-GTP.

137 We demonstrate that Rheb GTPase (Ras homolog enriched in brain), which induc

138 Stable localization of the Rheb GTPase to lysosomes is thought to be required for a

139 ionally controlled tumour protein (Tctp) and Rheb GTPase.

140 ses is a critical step for its activation by Rheb GTPase.

141 ts mTOR kinase signaling by inactivating the Rheb GTPase.

142 Rag and Rheb GTPases were central regulators of amino acid-depen

143 mTORC1 is activated on lysosomes by Rag and Rheb guanosine triphosphatases (GTPases) and drives bios

144 ling components, including raptor, S6K1, and Rheb, had been suggested in muscle maintenance, growth,

145 raction of FKBP38 with Bcl-2 is regulated by Rheb in a GTP-dependent manner.

146 ortant role in cancer cells, but the role of RHEB in cancer pathogenesis has not been shown.

147 ured cells, the interaction is controlled by Rheb in response to changes in amino acid and growth fac

148 Finally, ATF6 induced RHEB in response to growth factors, but not in response

149 estigated the functions of raptor, S6K1, and Rheb in the differentiation of C2C12 mouse myoblasts.

150 nversion prevents mTOR from interacting with Rheb in the late endosomal compartment.

151 The role of Rheb in the regulation of cell survival during ED has no

152 ab5CA, whereas hyperactivation of endogenous Rheb in TSC2-/- MEFs did not.

153 Functional testing of mutant RHEB in vertebrate animal models indicates pathway hyper

154 Expression of dMyc, but not of CycD/cdk4 or Rheb, in the FB diminishes the ability to retain Drosoph

155 expression of RAS homolog enriched in brain (RHEB) increased mTORC1 signaling, promoted a switch to a

156 te cell growth and glioma formation in a TSC/Rheb-independent fashion.

157 Collectively, these findings establish TSC/Rheb-independent mechanisms for mTOR-dependent glial cel

158 d Ras homolog enriched in brain-independent (RHEB-independent) mTORC1 activation.

159 ith the binding of 4EBP1 to mTORC1, inhibits Rheb-induced activation of mTORC1.

160 Rheb-induced tumor persistence and neoplastic molecular

161 IGF1 (insulin-like growth factor 1)-mediated RHEB induction, mTORC1 activation, and myocyte growth, a

162 Rheb inhibition causes mTORC1 inhibition, because forced

163 Rheb inhibits autophagy mostly through Atg7 depletion.

164 s in myogenesis, overexpression of raptor or Rheb inhibits C2C12 differentiation.

165 n 3T3-L1 adipocytes by ectopic expression of Rheb inhibits expression of ATGL and HSL at the level of

166 Moreover, GTP-bound Rheb interacts with BACE1 and degrades it through protea

167 utively active form of the mTORC1 regulator, Rheb, into HD mouse brain, alleviates mitochondrial dysf

168 skeletal muscle-specific knock-out mice for Rheb (iRhebKO) and TSC2 (iTSC2KO) and mechanically stimu

169 Rheb is a GTP-binding protein that promotes cell surviva

170 nvolves regulation of AMPK and p27, and that Rheb is a potential target for TSC/LAM therapy.

171 Rheb is a Ras family GTPase, which binds to and activate

172 RHEB is an activator of mTORC1 (mammalian/mechanistic ta

173 Thus, polyubiquitination of Rheb is an important post-translational modification, wh

174 Rheb is inactivated during cardiomyocyte (CM) glucose de

175 motes BACE1 accumulation, and this effect by Rheb is independent of its mTOR signaling.

176 Indeed, we found that Rheb is required for EGF-dependent mTOR activation in sp

177 C1 and supports its activation, while the Ub-Rheb is subjected to subsequent degradation.

178 Rheb is targeted to endomembranes via its C-terminal CAA

179 e domain of Ras homologue enriched in brain (Rheb) is tethered to cellular membranes through a prenyl

180 ompanied by inhibition of autophagy, whereas Rheb knockdown increased autophagy and CM survival.

181 hanced differentiation elicited by raptor or Rheb knockdown is accompanied by increased Akt activatio

182 ent in differentiation elicited by raptor or Rheb knockdown, suggesting that IRS1 is a critical media

183 that is increased by alcohol, targets mTOR, Rheb, LAMP1, and LAMP2 in the authophagy pathway.

184 Siah1 degrades Rheb leading to reduced mTOR signaling, while ketamine,

185 Finally, we demonstrate that Rheb levels are down-regulated in the AD brain, which is

186 from AML cells with the constitutively high Rheb levels.

187 Further systematic analysis of Rheb lipidation revealed that weak, nonselective, membra

188 ther farnesylthiosalicylic acid (FTS) blocks Rheb localization and function.

189 in of chromosome 7q36.1-q36.3 containing the RHEB locus, an overexpression of RHEB mRNA in several di

190 Rheb markedly sensitized transgenic epidermis to squamou

191 riven NSC proliferation results from tuberin/Rheb-mediated mammalian target of rapamycin (mTOR) hyper

192 t governs HSC quiescence and self-renewal by Rheb-mediated restriction of mTOR activity.

193 risation interface, poised to bind a pair of Rheb molecules at a similar separation to the pair in ac

194 taining the RHEB locus, an overexpression of RHEB mRNA in several different carcinoma histotypes, and

195 fering RNA (siRNA)-induced downregulation of Rheb, mTOR, or raptor, but also by siRNA for rictor.

196 3-kinase (PI3K)-dependent activation of the Rheb-mTOR pathway triggers the simultaneous local synthe

197 Our results indicate that TSC2-Rheb-mTOR signaling cooperates with the ephrin-Eph recep

198 -Tsc2 loss activated RalA/B independently of Rheb-mTOR signaling.

199 In conclusion, the Rheb-mTOR/raptor pathway negatively regulates myogenic d

200 loped based on NF1's central role in the RAS/RHEB/mTOR signal transduction pathway.

201 ograde axon degeneration is regulated by Akt/Rheb/mTor signaling pathways.

202 GTP binding and interaction with mTORC1 and Rheb-mTORC1 interaction in the Golgi.

203 demonstrate that the interplay between Tsc1-Rheb-mTORC1 signaling and Myc-dependent bioenergetic and

204 and the 3.4 angstrom structure of activated RHEB-mTORC1.

205 de the activation of a previously unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic bin

206 , which facilitates the binding of mTORC1 to Rheb on the lysosome and is another crosstalk between th

207 However, how the mTORC1 interacts with Rheb on the lysosome remains elusive.

208 expressing either constitutively active (ca) Rheb or a caRagB.caRagC complex, and coexpression of the

209 l region; however, little is known about how Rheb or other GTPases interact with the membrane or how

210 ity of MiT/TFEs, whereas genetic deletion of Rheb or Rptor or prolonged pharmacologic mTORC1 inactiva

211 onal epidermal loss of the mTORC1 components Rheb or Rptor, mTORC1 loss of function unexpectedly resu

212 Rheb overexpression depletes BACE1 protein levels and re

213 Furthermore, Rheb overexpression in 293E activated mTORC1 signaling c

214 Third, conditional Tsc1 inactivation or Rheb overexpression in glial progenitors of Nf1(+/-) mic

215 , because forced activation of Rheb, through Rheb overexpression in vitro and through inducible cardi

216 vitro and through inducible cardiac-specific Rheb overexpression in vivo, restored mTORC1 activity.

217 Rheb overexpression increases phosphorylation on raptor

218 1 or Pten inactivation, but not Tsc1 loss or Rheb overexpression, increases astrocyte cell growth in

219 f raptor Ser(863) via the canonical PI3K/TSC/Rheb pathway in a rapamycin-sensitive manner.

220 increased in the co-localisation of mTOR and Rheb post exercise in both FED and CON.

221 The identified NRE2 and NRE3 on the Rheb promoter are important to Notch-dependent promoter

222 the Notch-responsive elements (NREs) on the Rheb promoter is a key event.

223 on, whereas the RNAi knockdown of endogenous Rheb promotes BACE1 accumulation, and this effect by Rhe

224 Inactivation of Rheb protects CMs during ED through activation of autoph

225 In contrast to allosteric activation by RHEB, Rag heterodimer binding does not change mTORC1 con

226 altered association of mTOR with RagB/RagC, Rheb, raptor, and PRAS40.

227 bromin) glial growth regulation requires TSC/Rheb (Ras homolog enriched in brain) control of mTOR fun

228 ively active variant of an mTORC1 activator, Rheb (Ras homolog enriched in brain), could not prevent

229 llular killing of P. aeruginosa by targeting Rheb (Ras homolog enriched in brain).

230 mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by

231 and chromatin immunoprecipitation identified RHEB (Ras homologue enriched in brain) as an ATF6 target

232 or of mTORC1 that acts through modulation of RHEB (Ras homologue enriched in brain).

233 he colocalization of mTOR and its activator, Rheb (Ras homology enriched in brain)-GTP, to a perinucl

234 gether, these data indicate that the TSC and Rheb regulate Notch-dependent cell-fate decision in Dros

235 vation of a previously unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic binding of Not

236 provide biochemical evidence that they mimic RHEB relieving auto-inhibition.

237 wever, the lysosome targeting mechanisms for Rheb remain unclear.

238 Importantly, inhibition of mTOR, or Rheb, rescues HSC defects in Sel1L knockout mice.

239 Moreover, adeno-associated virus 9- RHEB restored cardiac growth to ATF6 cKO mice subjected

240 The addition of Rheb results in a significant increase of binding of the

241 ta also suggest that while overexpression of rheb results in aberrant synaptic overgrowth, the overgr

242 sfection with Ras homolog enriched in brain (Rheb) revealed that a PKB-independent activation of mamm

243 Constitutively active Rheb (Rheb(CA)), the canonical activator of mTOR complex

244 ted with both AXIN2 (rs2240308 p = 0.03) and RHEB (rs2374261 p = 0.03).

245 strocyte hyperproliferation is unaffected by Rheb shRNA silencing.

246 ation inhibitor beta, which likely regulates RHEB shuttling between GDP-bound and GTP-bound forms.

247 that 4,4'-biphenol (5) selectively inhibits Rheb signaling and induces cell death suggesting that th

248 nch, independent of the conventional Akt/TSC/Rheb signaling axis.

249 cells leading to the activation of Notch and Rheb signaling in the recipient cells.

250 , cancer stem cell maintenance, and HIF/mTOR/RHEB signaling pathways under hypoxia, resulting in supp

251 Here we focus on mTORC1 and show that TSC/Rheb signaling promotes mTOR S1261 phosphorylation in an

252 via PLCgamma/DAG/PKC signaling, not via Akt/Rheb signaling.

253 reviously been predicted to be important for Rheb-signalling suppression.

254 that, in skeletal muscle, overexpression of Rheb stimulates a PI3K/PKB-independent activation of mTO

255 eraction with Ras homolog enriched in brain (Rheb) stimulates mTORC1's kinase activity.

256 refore investigated the relationship between Rheb subcellular localization and mTORC1 activation.

257 We used NMR methods to characterize Rheb tethered to nanodiscs, monodisperse protein-encapsu

258 ling, while ketamine, conversely, stabilizes Rheb that enhances mTOR signaling.

259 s of membrane-dependent signal regulation by Rheb that shed light on previously unexplained in vivo p

260 b and Notch1 esRNA, in AML cells depleted of Rheb that were treated with the exosomes purified from A

261 tase E (INPP5E) and the GTP-binding protein (Rheb) that cargo sorting depends on the affinity towards

262 in (mTOR) and Ras homolog enriched in brain (Rheb), that initiate autophagy, correlated with increase

263 ase-activating protein (GAP) activity toward Rheb, this complex inhibits the mechanistic target of ra

264 RC1 inhibition, because forced activation of Rheb, through Rheb overexpression in vitro and through i

265 through the Rag complex and insulin through Rheb to achieve coordinate activation of mTORC1.

266 nsient membrane interactions optimally allow Rheb to activate mTORC1 signaling.

267 Using overexpression of Rheb to activate TORC1 and Rictor plus Sin1 to augment T

268 Notch cooperates with Rheb to block cell differentiation via similar mechanism

269 Further, Tsc1 signaled through Rheb to down-regulate mTORC1 for proper DC development,

270 ostinjury to express a constitutively active Rheb to enhance their intrinsic growth potential, transp

271 (ER) localization, constitutively targeting Rheb to ER membranes did not support mTORC1 activation.

272 ynergistic genetic interaction with Tctp and Rheb to impair tissue growth.

273 e complex, casts light on the recruitment of Rheb to the TSCC, and also hints at functional higher or

274 nd the GTPase Ras homolog enriched in brain (Rheb) to induce regrowth of axons after they have been d

275 uirement for amino acid sensing via Slimfast/Rheb/TOR complex 1.

276 By rapidly infiltrating tumors, RHEB-transduced T cells significantly reduced the emerge

277 sequencing efforts have identified recurrent Rheb Tyr35Asn mutations in kidney and endometrial carcin

278 mino acids enhance the polyubiquitination of Rheb (Ub-Rheb), which shows a strong binding preference

279 rexpression of the small GTP-binding protein RheB under nutrient starvation.

280 After farnesylation, Rheb undergoes two additional CAAX-signaled processing s

281 inoma histotypes, and an association between RHEB upregulation and poor prognosis in breast and head

282 arnesylation of the C-terminal CaaX motif on Rheb was essential for Rheb-dependent mTORC1 activation.

283 Surprisingly, we found that Rheb was undetectable at lysosomes.

284 PTOR, together with their upstream activator Rheb, was sufficient to provide TORC1 activity and stimu

285 a structure of mTORC1 bound to its activator Rheb, we developed a model of active mTORC1 docked on th

286 ity to interact directly with K-Ras and that Rheb weakly binds to bisphenol A (10) and 4,4'-biphenol

287 tors activate Ras homolog enriched in brain (Rheb), which in turn activates mTORC1 at the lysosome.

288 s enhance the polyubiquitination of Rheb (Ub-Rheb), which shows a strong binding preference for mTORC

289 Overexpression of Rheb, which activates mTOR independently of mTOR localiz

290 ignaling, but does not inhibit the effect of Rheb, which directly binds and activates mTORC1.

291 ignaling, but does not inhibit the effect of Rheb, which directly binds to and activates mTORC1.

292 mTORC1 is regulated by the small GTPase Rheb, which in turn is regulated by the GTPase-activatin

293 PLD is a downstream target of the GTPase Rheb, which is turned off in response to AMPK via the tu

294 results argue against stable interactions of Rheb with lysosomes and instead that transient membrane

295 Finally, we demonstrate that Rheb-WT can bind AMPK to facilitate AMPK activation, whe

296 Here we show that Rheb-Y35N causes not only constitutive mTORC1 activation

297 AMPK to facilitate AMPK activation, whereas Rheb-Y35N competitively binds AMPK, impairing AMPK phosp

298 Furthermore, Rheb-Y35N inhibits AMPKalpha activation in response to n

299 In summary, our findings indicate that Rheb-Y35N is a dominantly active tumor driver that activ

300 Rheb-Y35N transforms NIH3T3 cells, resulting in aggressi