Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor
Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor
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DOI：
10.1016/s0092-8674(00)80595-4
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发表时间：
1999-03-19
期刊：
影响因子：
64.5
通讯作者：
Greenberg, ME
中科院分区：
文献类型：
--
作者：
Brunet, A;Bonni, A;Greenberg, ME
存活因子可以通过激活丝氨酸/苏氨酸激酶Akt以转录非依赖性方式抑制细胞凋亡，所述丝氨酸/苏氨酸激酶Akt然后磷酸化并灭活细胞凋亡机制的组分，包括BAD和胱天蛋白酶9。在这项研究中，我们证明，Akt也调节FKHRL 1，叉头家族的转录因子的成员的活动。在存活因子存在下，Akt使FKHRL 1磷酸化，导致FKHRL 1与14-3-3蛋白结合并使FKHRL 1保留在细胞质中。生存因子戒断导致FKHRL 1去磷酸化、核转位和靶基因激活。在细胞核内，FKHRL 1最有可能通过诱导对细胞死亡至关重要的基因（如Fas配体基因）的表达来触发细胞凋亡。
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.