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SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth.
- Source :
-
Cell metabolism [Cell Metab] 2008 Sep; Vol. 8 (3), pp. 224-36. - Publication Year :
- 2008
-
Abstract
- Cell growth (accumulation of mass) needs to be coordinated with metabolic processes that are required for the synthesis of macromolecules. The PI3-kinase/Akt signaling pathway induces cell growth via activation of complex 1 of the target of rapamycin (TORC1). Here we show that Akt-dependent lipogenesis requires mTORC1 activity. Furthermore, nuclear accumulation of the mature form of the sterol responsive element binding protein (SREBP1) and expression of SREBP target genes was blocked by the mTORC1 inhibitor rapamycin. We also show that silencing of SREBP blocks Akt-dependent lipogenesis and attenuates the increase in cell size in response to Akt activation in vitro. Silencing of dSREBP in flies caused a reduction in cell and organ size and blocked the induction of cell growth by dPI3K. Our results suggest that the PI3K/Akt/TOR pathway regulates protein and lipid biosynthesis in an orchestrated manner and that both processes are required for cell growth.
- Subjects :
- Animals
Cell Enlargement drug effects
Cell Nucleus metabolism
Cells, Cultured
Drosophila
Gene Expression drug effects
Lipids biosynthesis
Proto-Oncogene Proteins c-akt antagonists & inhibitors
RNA Interference
Signal Transduction drug effects
Sirolimus pharmacology
Drosophila Proteins metabolism
Proto-Oncogene Proteins c-akt metabolism
Sterol Regulatory Element Binding Protein 1 metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-7420
- Volume :
- 8
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 18762023
- Full Text :
- https://doi.org/10.1016/j.cmet.2008.07.007