mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway
Author(s)Peterson, Timothy R.; Sengupta, Shomit S.; Harris, Thurl E.; Carpenter, Anne E.; Kang, Seong A.; Balderas, Eric; Guertin, David A.; Madden, Katherine L.; Finck, Brian N.; Sabatini, David M.; Kang, Seong A.; Peterson, Timothy Richard; Sengupta, Shomit; Sabatini, David; ... Show more Show less
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The nutrient- and growth factor-responsive kinase mTOR complex 1 (mTORC1) regulates many processes that control growth, including protein synthesis, autophagy, and lipogenesis. Through unknown mechanisms, mTORC1 promotes the function of SREBP, a master regulator of lipo- and sterolgenic gene transcription. Here, we demonstrate that mTORC1 regulates SREBP by controlling the nuclear entry of lipin 1, a phosphatidic acid phosphatase. Dephosphorylated, nuclear, catalytically active lipin 1 promotes nuclear remodeling and mediates the effects of mTORC1 on SREBP target gene, SREBP promoter activity, and nuclear SREBP protein abundance. Inhibition of mTORC1 in the liver significantly impairs SREBP function and makes mice resistant, in a lipin 1-dependent fashion, to the hepatic steatosis and hypercholesterolemia induced by a high-fat and -cholesterol diet. These findings establish lipin 1 as a key component of the mTORC1-SREBP pathway.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research; Koch Institute for Integrative Cancer Research at MIT
Peterson, Timothy R., Shomit S. Sengupta, Thurl E. Harris, Anne E. Carmack, Seong A. Kang, Eric Balderas, David A. Guertin, et al. “mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway.” Cell 146, no. 3 (August 2011): 408–420. © 2011 Elsevier Inc.
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