Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor

被引：5563

作者：

Brunet, A

Bonni, A

Zigmond, MJ

Lin, MZ

Juo, P

Hu, LS

Anderson, MJ

Arden, KC

Blenis, J

Greenberg, ME

机构：

[1] Childrens Hosp, Div Neurosci, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[4] Univ Calif San Diego, Ludwig Inst Canc Res, San Diego, CA 92093 USA

来源：

CELL | 1999年 / 96卷 / 06期

关键词：

D O I：

10.1016/S0092-8674(00)80595-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase Akt, which then phosphorylates and inactivates components of the apoptotic machinery, including BAD and Caspase 9. In this study, we demonstrate that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors. In the presence of survival factors, Akt phosphorylates FKHRL1, leading to FKHRL1's association with 14-3-3 proteins and FKHRL1's retention in the cytoplasm. Survival factor withdrawal leads to FKHRL1 dephosphorylation, nuclear translocation, and target gene activation. Within the nucleus, FKHRL1 triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene.

引用

页码：857 / 868

页数：12

共 44 条

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