SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth

被引：1136

作者：

Porstmann, Thomas ^{[1
]}

Santos, Claudio R. ^{[1
]}

Griffiths, Beatrice ^{[1
]}

Cully, Megan ^{[2
]}

Wu, Mary ^{[3
]}

Leevers, Sally ^{[4
]}

Griffiths, John R. ^{[5
]}

Chung, Yuen-Li ^{[6
,7
]}

Schulze, Almut ^{[1
]}

机构：

[1] Gene Express Anal Lab, London WC2A 3PX, England

[2] Signal Transduct Lab, London WC2A 3PX, England

[3] Dev Signalling Lab, London WC2A 3PX, England

[4] Can Res UK London Res Inst, London WC2A 3PX, England

[5] Li Ka Shing Ctr, Cancer Res UK Cambridge Res Inst, Cambridge CB2 0RE, England

[6] Inst Canc Res, Canc Res UK Biomed Magnet Resonance Res Grp, Surrey, England

[7] Royal Marsden Hosp, Surrey, England

来源：

CELL METABOLISM | 2008年 / 8卷 / 03期

关键词：

D O I：

10.1016/j.cmet.2008.07.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：224 / 236

页数：13

共 57 条

[1] Promoter analysis of the mouse sterol regulatory element-binding protein-1c gene [J].