SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth.
SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth.
复制标题
DOI：
10.1016/j.cmet.2008.07.007
复制
发表时间：
2008-09
期刊：
影响因子：
29
通讯作者：
Schulze A
中科院分区：
文献类型：
--
作者：
Porstmann T;Santos CR;Griffiths B;Cully M;Wu M;Leevers S;Griffiths JR;Chung YL;Schulze A
细胞生长（质量的积累）需要与大分子合成所需的代谢过程相协调。PI 3-激酶/Akt信号通路通过激活雷帕霉素靶标的复合物1（TORC 1）诱导细胞生长。在这里，我们表明Akt依赖性脂肪生成需要mTORC 1活性。此外，成熟形式的固醇反应元件结合蛋白（SREBP 1）的核积累和SREBP靶基因的表达被mTORC 1抑制剂雷帕霉素阻断。我们还表明，沉默SREBP阻断Akt依赖的脂肪生成，并减弱细胞大小的增加，在体外响应Akt激活。果蝇中dSREBP的沉默导致细胞和器官尺寸减小，并阻断dPI 3 K对细胞生长的诱导。我们的研究结果表明，PI 3 K/Akt/TOR途径以协调的方式调节蛋白质和脂质的生物合成，这两个过程都是细胞生长所必需的。
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.
登录
查看更多内容
影响因子：
3.3
作者：
Edinger, AL;Thompson, CB
通讯作者：
Thompson, CB
影响因子：
8
作者：
Bauer, DE;Hatzivassiliou, G;Thompson, CB
通讯作者：
Thompson, CB
影响因子：
4.8
作者：
Hirano, Y;Yoshida, M;Sato, R
通讯作者：
Sato, R
影响因子：
11.4
作者：
Leevers, SJ;Weinkove, D;Waterfield, MD
通讯作者：
Waterfield, MD
影响因子：
4.8
作者：
Bennett, MK;Toth, JI;Osborne, TF
通讯作者：
Osborne, TF