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mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway

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Peterson, Timothy R., Sengupta, Shomit S., Harris, Thurl E., Carmack, Anne E., Kang, Seong A., Balderas, Eric, Guertin, David A., Madden, Katherine L., Carpenter, Anne E., Finck, Brian N., Sabatini, David M.·2011·Cell
DOI 10.1016/j.cell.2011.06.034
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Abstract

SUMMARY 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.

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Metadata

Authors
Peterson, T. R., Sengupta, S. S., Harris, T. E., Carmack, A. E., Kang, S. A., Balderas, E., Guertin, D. A., Madden, K. L., Carpenter, A. E., Finck, B. N., & Sabatini, D. M.
Venue
Cell
Publisher
Elsevier BV
Published
2011-08
Volume
146
Issue
3
Pages
408-420
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2011.06.034
OpenAlex
W2144235090
Cited by
1,229
References
12
FWCI
27.51
Type
journal article
Language
en
Open access
bronze
Licence
Funders
  • National Institutes of Health (R01 AI47389, R01 CA103866, R01 GM089652-01)
  • American Diabetes Association
  • W. M. Keck Foundation
  • LAM Foundation
  • Jane Coffin Childs Memorial Fund for Medical Research (RO1 DK078187)

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CoChat. (2026). Citation check: mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway. https://app.cochat.ai/papers/10.1016/j.cell.2011.06.034
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Peterson, T. R., Sengupta, S. S., Harris, T. E., Carmack, A. E., Kang, S. A., Balderas, E., Guertin, D. A., Madden, K. L., Carpenter, A. E., Finck, B. N., & Sabatini, D. M. (2011). mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway. Cell. https://doi.org/10.1016/j.cell.2011.06.034

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