IndraLab

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TSC2 inhibits RPS6KB1. 10 / 28
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"The tuberin S939A and T1462A mutant but not wild-type tuberin also significantly reduces S6K1 activity from cells growing in full serum."
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"Finally, we analyzed whether Rheb mediated activation of S6K1 is affected by a pathologic mutation in human TSC2, which fails to inhibit S6K1 activation.If the effects of TSC1/2 loss of function mutat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12820960
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"Our study demonstrates that IFNbeta dependent activation of STATs and p38 MAPK is not sufficient to fully inhibit proliferation of cells with TSC2 dysfunction and that TSC2 dependent inhibition of mTOR and S6K1 cooperates with IFNbeta in inhibiting human LAM and TSC2-null ELT3 cell proliferation."
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"It will be of great interest to determine the molecular nature of S6K1 inhibition by the tuberin-hamartin complex in the absence of mitogenic stimuli."
12150915
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"In HT29 colon tumoral cells XREF_BIBR, AMPK activation by synthetic molecules or polyphenolic compounds was shown to activate TSC2, which in turn inhibits TORC1 and mTOR and p70S6K."
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"These data demonstrate that tuberin negatively regulates the activity of S6 and p70S6K specifically, and suggest a potential mechanism for abnormal cell growth in LAM."
12045200
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"Incubation of RMCs with 1,25 (OH) 2 D 3 for 48 h increased VDR expression (p < 0.05), restored the expression of TSC1 and TSC2 and 4E-BP1, and blocked the aberrant upregulation of Rheb, mTOR and p70S6K."
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"Over-expression of TSC1 and TSC2 also markedly inhibited S6K1, positioning TSC1 and TSC2 upstream of S6K1."
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"In TSC2-/- MEF and TSC2-/- rat cells, loss of tuberin resulted in the constitutive activation of S6K1 leading to the hyperphosphorylation of ribosomal protein S6 [71,72]."
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"Moreover, in mammalian cells in culture, co-overexpression of TSC1 and TSC2 prevents amino acid dependent activation of S6K1 [XREF_BIBR]."
15507151
TSC2 bound to TSC1 inhibits RPS6KB1. 4 / 4
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"Loss of TSC2 GAP activity or disruption of the TSC1 and TSC2 complex dysregulates S6K1 activation, which leads to abnormal cell proliferation associated with LAM disease."
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"This phosphorylation inhibits the tuberin and hamartin complex, thereby relieving its inhibition of S6K1."
12150915
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"Together, these studies imply that the tuberin and hamartin complex functions to inhibit S6K1 activation.We therefore tested if wild-type tuberin or tuberin S939A and T1462A had any effect on phosphor[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12150915
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"Furthermore, both mouse and Drosophila genetic studies have suggested that the tuberin and hamartin complex functions to inhibit S6K1 (Kwiatkowski et al., 2002; Potter et al., 2001; Tapon et al., 2001[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12150915
Mutated TSC2 inhibits RPS6KB1. 3 / 3
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"Finally, a tuberin mutant lacking the major PI3K dependent phosphorylation sites blocked the activation of S6K1, suggesting a means by which the PI3K-Akt pathway regulates S6K1 activity [XREF_BIBR]."
19384426
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"Furthermore, we find that overexpression of a tuberin mutant lacking the major Akt phosphorylation sites can inhibit growth factor induced activation of S6K1."
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"Finally, we find that a tuberin mutant lacking the major PI3K dependent phosphorylation sites can block the activation of S6K1, suggesting a means by which the PI3K-Akt pathway regulates S6K1 activity."
12150915
TSC2 inhibits RPS6KB1. 1 / 1
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"Tuberin interferes with insulin-like growth factor-1-induced BAD Ser136 phosphorylation and cell survival. Our work proposes a model in which tuberin-mediated inhibition of p70S6K activates BAD to heterodimerize with BCL-2 and BCL-XL to promote apoptosis. A mutation of TSC2--as it occurs in TSC patients--attenuates this proapoptotic potential, underscoring the relevance of our findings for human pathophysiology."
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TSC2 inhibits RPS6KB1-S6K. 1 / 1
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"siRNA mediated knockdown of both TSC2 and Rictor elevates p70 S6K activation and induces differentiation of hESCs."
20698768
TSC2-S939A inhibits RPS6KB1. 1 / 1
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"The tuberin S939A and T1462A mutant but not wild-type tuberin also significantly reduces S6K1 activity from cells growing in full serum."
12150915
TSC2 phosphorylated on S1798 inhibits RPS6KB1. 1 / 1
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bel
"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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