An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss - Nature Communications

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An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss - Nature Communications
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Taming overactive molecular signaling in renal cell cancer NatureComms

The mechanistic target of rapamycin complex 1 integrates inputs from growth factors and nutrients, but how mTORC1 autoregulates its activity remains unclear. The MiT/TFE transcription factors are phosphorylated and inactivated by mTORC1 following lysosomal recruitment by RagC/D GTPases in response to amino acid stimulation.

hypophosphorylation and activation upon feeding. phosphorylation in-null renal cells is partially restored by destabilization of the lysosomal folliculin complex induced by FLCN mutants and is fully rescued by forced lysosomal localization of the FLCN:FNIP2 dimer.

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