IndraLab

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TSC2 decreases the amount of TSC2. 14 / 14
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"A previous study in smooth muscle like cells from a patient with tuberous sclerosis showed that epigenetic regulation of the TSC2 promoter through methylation represses TSC2 expression."

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"We further show that Gankyrin overexpression accelerated TSC2 degradation, while knockdown in a panel of colorectal cancer (CRC) cell lines, cell line derived xenografts and CRC patient derived xenograft (PDX) tumors delayed TSC2 degradation, restored the TSC2 protein level, and inhibited mTORC1 signaling and CRC growth."

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"While we find that activation of N is sufficient and required for repression of TSC2 protein in EBs in vivo, our S2 studies indicate that the turnover rate of the TSC2 protein also has to be increased to achieve rapid reduction of TSC2 levels."

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"TSC2 RNAi significantly decreased endogenous TSC2 protein levels, but had no effect on the unrelated protein MEK2."

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"Su (H)-mediated transcriptional repression of gigas and Tsc2 was thus a plausible mechanism for N induced repression of TSC2 expression in EBs."

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"Inhibition of tuberin expression by Tsc2 antisense greatly reduces the ability of TGF-beta to transcriptionally regulate p21 (CIP), p27 (KIP), and cyclin A leading to an abrogation of the antiproliferative effects of TGF-beta1."

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"The TSC2 shRNA strongly reduced endogenous TSC2 expression in all MEFs (XREF_FIG)."

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"LAM and TSC cells bear a germline mutation in exon 21 of TSC2 and do not express tuberin because of an epigenetic silencing of the TSC2 second allele that confirms our previously published evidence that an epigenetic alteration of TSC2 can cause the loss of tuberin in TSC cells [XREF_BIBR]."

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"Moreover, transfection of TSC2 and tuberin siRNA into PC-3 cells inhibited the expression of tuberin, mildly increased the basal phosphorylation level and only marginally counteracted curcumin mediated inhibition (XREF_FIG), while showed no effect on the basal level or curcumin mediated inhibition of the phosphorylation of Akt."

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"First, western blotting validated that the expression of TSC2 was effectively decreased by TSC2 targeted shRNA (XREF_FIG)."

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"Furthermore, shRNA mediated CUL4B knockdown caused an upregulation of TSC2 or cyclin E. XLID mutant (R388X), (R572C) or (V745A) CUL4B did not downregulate protein expression of TSC2 or cyclin E in neocortical neurons."

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"In addition, previous studies in human neuroblastoma cell lines have demonstrated that tuberin AS-constructs reduce tuberin expression and alter cell cycle dynamics."

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"Consistent with these observations, NT3 mRNA expression was reduced but trkC mRNA expression was increased in vitro in human NTera2 neurons (NT2N) transfected with a tuberin antisense construct that reduced tuberin expression."

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"It has been shown that an epigenetic alteration of TSC2 can cause the loss of tuberin in TSC cells."