MassIVE MSV000100927

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Genetically targetable mTORC1 inhibitor reveals transcriptional control by nuclear mTORC1

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Description

The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a nutrient sensor which integrates diverse inputs to regulate protein translation and cell growth. While mTORC1 is activated on the lysosome in the classical model, it has become increasingly clear that this multifaceted signaling complex is active at various subcellular locations, such as the plasma membrane and nucleus. However, what specific functions mTORC1 serves at these different subcellular locations and how its signaling is compartmentalized are not well understood. To interrogate subcellular pools of mTORC1, we developed TerminaTOR, a genetically encodable inhibitor of mTORC1 that can be targeted to specific subcellular locations. When TerminaTOR is directed to the lysosome, it inhibits canonical lysosomal mTORC1 activity, leading to the induction of autophagy. On the other hand, TerminaTOR targeted to the nucleus specifically inhibits nuclear mTORC1 activity, uncovering non- canonical roles of nuclear mTORC1 in regulating the transcription of CCAAT motif- containing genes. Thus, mTORC1 exhibits functional spatial compartmentalization, and TerminaTOR serves as a powerful tool for unraveling spatially regulated functions of mTORC1 across different scales. [doi:10.25345/C50R9MJ04] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: MTOR ; signaling ; nuclear signaling ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Jin Zhang, UCSD, USA
Submitting User: sammyers
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