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
DownloadPeterson-2011-mTOR Complex 1 Regul.pdf (1.537Mb)
PUBLISHER_POLICY
Publisher Policy
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Terms of use
Metadata
Show full item recordAbstract
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.
Date issued
2011-08Department
Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research; Koch Institute for Integrative Cancer Research at MITJournal
Cell
Publisher
Elsevier
Citation
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.
Version: Final published version
ISSN
00928674
1097-4172