@article{3ef042b422374ecc981b1c28c5fc15f1,
title = "RIPK1 Promotes Energy Sensing by the mTORC1 Pathway",
abstract = "RIPK1 scaffold activity is known to have a pro-survival role in TNFα signaling. Najafov et al. discover an unexpected role for RIPK1 scaffold activity in mediating mTORC1 inhibition by AMPK during energetic stress. Mechanistic studies reveal that RIPK1 is involved in regulating TSC2 phosphorylation at Ser1387 by AMPK. Reduced phosphorylation of this site in RIPK1-deficient cells results in a chronically elevated mTORC1 activity and lysosomal dysfunction.",
keywords = "AMPK, CASP8, MLKL, RIPK1, RIPK3, TSC2, lysosome, mTORC1, neonatal lethality",
author = "Ayaz Najafov and Luu, {Hoang Son} and Mookhtiar, {Adnan K.} and Lauren Mifflin and Xia, {Hong guang} and Amin, {Palak P.} and Alban Ordureau and Huibing Wang and Junying Yuan",
note = "Funding Information: This work was supported in part by the Ludwig Cancer Center at Harvard Medical School . We thank the Nikon Imaging Center at Harvard Medical School for assistance with microscopy. We are grateful to Dr. Vishva Dixit for RIPK3 knockout mice, Dr. Douglas R. Green for FADD knockout mice, Dr. Michelle Kelliher for RIPK1 knockout mice, Dr. Benoit Viollet for AMPK knockout MEFs, and Dr. Gerta Hoxhaj for TSC2 knockout MEF lysates. Funding Information: Plasmids were transformed into in-house-made chemically-competent DH5α E. coli cells. Plasmid purifications and extractions were performed using QIAprep Spin Miniprep Kit (QIAGEN), QIAquick Gel Extraction Kit (QIAGEN), and Plasmid Maxi or Midi kits (QIAGEN). Sequencing was done with an ABI3730xl DNA analyzer at the DNA Resource Core of Dana-Farber/Harvard Cancer Center (funded in part by NCI Cancer Center support grant 2P30CA006516-48). Funding Information: This work was supported in part by the Ludwig Cancer Center at Harvard Medical School. We thank the Nikon Imaging Center at Harvard Medical School for assistance with microscopy. We are grateful to Dr. Vishva Dixit for RIPK3 knockout mice, Dr. Douglas R. Green for FADD knockout mice, Dr. Michelle Kelliher for RIPK1 knockout mice, Dr. Benoit Viollet for AMPK knockout MEFs, and Dr. Gerta Hoxhaj for TSC2 knockout MEF lysates. A.N. and J.Y. conceived the project, designed the experiments, analyzed the data, and wrote the manuscript. A.N. performed most of the experiments. H.S.L. A.K.M. P.A. L.M. H.X. and A.O. performed and assisted with experiments. H.S.L. and L.M. assisted with the manuscript. H.W. provided samples or reagents. Junying Yuan is a consultant for Denali Therapeutics and Sanofi S.A. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = jan,
day = "21",
doi = "10.1016/j.molcel.2020.11.008",
language = "English (US)",
volume = "81",
pages = "370--385.e7",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}