IndraLab

Statements

TSC2 inhibits MTOR. 10 / 436
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"Identification of mutations in the tuberous sclerosis 1 (TSC1) and TSC2 genes producing constitutive activation of the mammalian target of rapamycin (mTOR) pathway presents an opportunity for targeted therapy."
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"TSC2-depleted tumor cells had disrupted mTOR regulation following CTL attack, which was associated with enhanced cell death."
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"In tumors that retained TSC2 expression, phosphorylation of tuberin at S939 was observed with a high frequency, indicating that mTOR repression by TSC2 had been relieved via AKT phosphorylation of this tumor suppressor."
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"These results suggest that phosphorylation of TSC2 by GSK3 increases the ability of TSC2 to inhibit mTOR signaling.Previously, we found that mTOR activity contributed to cell apoptosis under glucose s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"For instance, lncRNA MALAT1 can recruit EZH2 to induce H3K27me3 modification in the TSC2 promoter region, thus repressing its transcription, while TSC2 overexpression inhibits mTOR signaling and activates autophagy."
33335796
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"Our findings showed that either TSC2 deletion or TSC2 mutant could lead to TSC2 loss-of-function and hyperactivation of mTOR signaling."
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"In such cases loss of TSC1 and TSC2 would be required to activate mTOR."
18759130
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"All these observations are consistent with our model that TSC2 acts downstream of AMPK to inhibit mTOR."
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"Suppression of mTOR by tuberin takes place only when tuberin is tethered to the membrane."
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"In addition, the activation of AMPK can phosphorylate TSC2 and the activated TSC2 can suppress mTOR complex 1 (mTORC1) to induce autophagy XREF_BIBR, XREF_BIBR."
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TSC2 bound to TSC1 inhibits MTOR. 10 / 18
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"The TSC1 and TSC2 complex is the only known GTPase for Rheb, serving to reduce Rheb-GTP levels, and thereby inhibit the activation of mTOR."
21618507
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"Once activated, AKT mediated phosphorylation of TSC2 (tuberous sclerosis complex 2) inhibits the TSC1 and TSC2 complex function, and thus activates mTOR signaling."
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"The TSC1 and TSC2 complex normally inhibits mTOR activity, with loss of function mutations resulting in overactive mTOR and consequential increased protein synthesis and decreased protein degradation [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"40 TSC1 and TSC2 complex inhibits mTOR activity by activating the GTPase activity of Ras homologue enriched in brain, and both Akt and AMPK converged at TSC1 and TSC2 to regulate mTOR activity."
21618507
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"Under the condition that AMPK is activated, AMPK phosphorylates tuberous sclerosis complex 2 (TSC2) and increases the activity of the TSC1 and TSC2 complex to inhibit mTOR."
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"The TSC1 and TSC2 complex inactivates Rheb to inhibit mTOR signaling, which would lead to autophagy."
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"The TSC1 and TSC2 heterodimer inhibits mTOR function through Rheb inactivation."
18443221
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"Overall, these results demonstrate that activation of p38 inhibits the TSC1 and TSC2 complex allowing mTOR activation potentially via MK2 dependent phosphorylation of TSC2 at Ser 1210."
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"CTuberin binds to hamartin and Rheb and inhibits mTOR activation."
| PMC
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"Interestingly, our RNA sequencing analysis of Etv TKO mutant lenses showed significant down-regulation of Tsc2, which forms a heterodimer with Tsc1 to inhibit mTOR activity (Figure 3C)."
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Mutated TSC2 inhibits MTOR. 7 / 7
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"In addition in the Eker rat model, a mutant Tsc2 gene that fails to inhibit mTOR is still able to suppress tumourigenesis, and administration of rapamycin reduces the development of macroscopic tumours while having no effect on the number of microscopic precursor lesions."
21387562
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"After the review of the literature and our retrospective examination of 20 lesions, we observed three common and constant components, more or less present in all varieties of TSC cutaneous hamartomas (AF, SP, FCP and FCCH):-abundant thickened collagen, associated with adnexal involvement (concentric fibrosis)-vascular hyperplasia,-cellular proliferation of fibroblasts.TSC1 or TSC2 mutations cause a defect in mTOR inhibition and promote cell proliferation but also angiogenesis and vessel modification due to increased production of VEGF by fibroblastic cells carrying the mutation [3,29]."
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"Here, we report that in rat embryonic fibroblasts, activation of mammalian target of rapamycin complex 1 by a Tsc2 mutation or overexpression of a constitutively active mutant Rheb overrides the absence of the anchorage and stabilizes Cdc6 at least partly via activating Cdk4/6 that induces Emi1, an APC/C (Cdh1) ubiquitin ligase inhibitor."
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"XREF_BIBR TSC1 and TSC2 mutations impair regulation of the mTOR pathway and cause tuberous sclerosis."
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"The mutation of TSC2 may induce the formation of tumours by affecting mTOR inhibition."
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"TSC1 or TSC2 mutations cause Tuberous Sclerosis Complex (TSC), and lead to mechanistic target of rapamycin (mTOR) hyperactivation evidenced by hyperphosphorylation of ribosomal S6 protein and 4 elongation factor binding protein (4E-BP1)."
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"Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1)."
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TSC2 bound to RHEB inhibits MTOR. 2 / 2
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"TSC2 is inactivated by phosphorylation, resulting in accumulation of GTP bound Rheb that activates the mechanistic target of rapamycin (mTOR) that is in a complex with regulatory associated protein of mTOR (Raptor) termed mTORC1."
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"CTuberin binds to hamartin and Rheb and inhibits mTOR activation."
| PMC
Phosphorylated TSC2 inhibits MTOR. 2 / 2
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"Moreover, the phosphorylated TSC2 can participate in stimulating cell growth and suppress mTOR signaling (69)."
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"In this regard, LKB1 mediated AMPK activation leads to accumulation of phosphorylated TSC2 [XREF_BIBR], which inhibits mTOR signaling by blocking phosphorylation of its two key translational regulators, p70 ribosomal S6 kinase 1 (S6K) and eukaryote initiation factor 4E binding protein 1 (4E-BP1) (XREF_FIG) [XREF_BIBR, XREF_BIBR]."
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TSC2 bound to ARD1 inhibits MTOR. 1 / 1
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"Here, we demonstrate that arrest defective protein 1 (ARD1) physically interacts with, acetylates, and stabilizes TSC2, thereby repressing mTOR activity."
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TSC2 bound to TSC2 inhibits MTOR. 1 / 1
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"Hamartin and tuberin, the TSC1 and TSC2 gene products, form a complex that inhibits mammalian target of rapamycin (mTOR) in a conserved cellular signaling pathway (PI3kinase- Akt-mTOR pathway) that regulates nutrient uptake, growth and protein translation [9], [10], [11]."
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TSC2 phosphorylated on S1798 inhibits MTOR. 1 / 1
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"TSC2 S1798A mutant.Thi s mutant was used to prove that RSK-dependent phosphorylation of tuberin on Ser1798 inhibits its potential to turn off Rheb and to downregulate the activities of mTOR and p70S6K.Mu tation of Ser1798 inhibited most of tuberin phosphorylation and inactivation by RSK (Roux et al., 2004).Invest igating PARP cleavage, caspase 3 cleavage, the percentage of HOPI-positive cells and the percentage of subG1 cells demonstrated that the cell survival effects of activated Ras over tuberin-induced apoptosis are significantly diminished by this mutation in TSC2 (Figures 5a–c)."
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TSC2-L1511H inhibits MTOR. 1 / 1
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"Therefore, in both assays, the TSC2 I820del and L1511H variants were unable to inhibit mTOR, indicating that both these variants are pathogenic, while the TSC2 R1772C and T993M variants were just as active as wild-type TSC2 and are therefore not pathogenic amino acid substitutions."
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TSC2 phosphorylated on T1462 inhibits MTOR. 1 / 1
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"Upon activation, AKT not only activates mTOR signaling by direct phosphorylation at Ser2448 of mTOR but also catalyzes phosphorylation at Thr1462 of TSC2 that inhibits TSC1/TSC2 complexes, a master negative regulator of mTOR (148, 149)."
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TSC2 bound to ENPP1 inhibits MTOR. 1 / 1
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"PC1 interacts with tuberin to suppress mTOR and activation of the downstream translation initiation factor eIF4E."
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TSC2 inhibits phosphorylated MTOR. 1 / 1
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"The extracellular signal regulated-kinase1/2 (ERK1/2) pathway and AMP activated protein kinase (AMPK) have also been reported to positively regulate autophagy [30] by activating Tuberous sclerosis com[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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