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Publication : mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway.

First Author  Peterson TR Year  2011
Journal  Cell Volume  146
Issue  3 Pages  408-20
PubMed ID  21816276 Mgi Jnum  J:174681
Mgi Id  MGI:5140624 Doi  10.1016/j.cell.2011.06.034
Citation  Peterson TR, et al. (2011) mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway. Cell 146(3):408-20
abstractText  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. PAPERCLIP:
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