IndraLab

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TSC1 inhibits RPS6KB1. 10 / 11
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"Furthermore, overexpression of Hamartin and Tuberin blocked S6K1 activation upon the readdition of amino acids to nutrient starved cells [18, 19]."
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"In cancer, there is an increase in the activity of PI3K-AKT axis, and TSC1 and TSC2 is inhibited by AKT, allowing mTORC1 activation and subsequently activation of P70S6K1 and EIF4e."
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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."
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"Hamartin with alanine mutations in the three cyclin dependent kinase 1 phosphorylation sites increased the inhibition of p70S6 kinase by the hamartin and tuberin complex."
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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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"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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"Loss of either Hamartin or Tuberin expression within cells resulted in constitutive S6K1 activation in the absence of amino acids [18]."
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"While investigators concluded that tuberin and hamartin inhibit insulin induced activation of the overexpressed wild-type S6K1, conflicting data exist concerning the effect of tuberin and hamartin on [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Hamartin with alanine mutations in the three cyclin-dependent kinase 1 phosphorylation sites increased the inhibition of p70S6 kinase by the hamartin-tuberin complex."
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"In HEK293 cells, overexpression of tuberin and hamartin attenuated basal, insulin-and Ras stimulated S6K1 activation [37,86]."
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Catalytically active TSC1 bound to TSC2 inhibits RPS6KB1. 1 / 1
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"Furthermore, in insulin- or serum-stimulated cells, activation of p70S6K is inhibited by expression of the Tsc1-Tsc2 complex [54,55]. This finding demonstrates that the introduction of a genetic inhibitor of mTOR, downstream of Akt1, inhibits the activation of p70S6K, adding genetic evidence for an Akt1-mTOR-p70S6K pathway."
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