The schematic depicting the canonical and non-canonical mTORC1 and necroptotic pathway. (IMAGE)
Caption
(A) Canonical mTORC1 pathway. Traditionally, mTORC1 is known to regulate protein synthesis and autophagy by phosphorylating its three major substrates: 4EBP1, S6K, and ULK1. (B) Non-canonical role of “RSK1–SGK1” pathway in necroptosis, indicated by blue arrow. Under necroptotic stimuli, TSC1 inhibition could lead to RIP3 and MLKL activation through mTORC1, finally leading to necroptosis through “4EBP1–eIF4E" and “RSK1–SGK1” pathway. (C) Canonical RIP3/MLKL-mediated necroptosis. In traditional necroptotic pathway, caspase-8 could suppress FADD/RIP1/RIP3/MLKL-dependent necroptosis.
Credit
Shuchao Wang, Yating Tan, Minghai Hu, Meijuan Wang, Lu Liang, Xing Luo, Dan Chen, Bing Jiang, Ceshi Chen, Jufang Huang, Kun Xiong
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