Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis
Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis
复制标题
DOI：
10.1016/s1097-2765(02)00776-1
复制
发表时间：
2003-01-01
期刊：
影响因子：
16
通讯作者：
Downward, J
中科院分区：
文献类型：
--
作者：
Basu, S;Totty, NF;Downward, J
我们使用亲和纯化方法鉴定蛋白激酶B/Akt的底物。以Akt依赖性方式与14-3-3结合的一种蛋白质在此显示为Yes相关蛋白（雅普），其在丝氨酸127处被Akt磷酸化，导致与14-3-3结合。Akt促进雅普定位于细胞质，导致其从细胞核丢失，在细胞核中其作为包括p73的转录因子的共激活因子发挥作用。DNA损伤后p73介导的Bax表达诱导需要雅普功能，并且通过雅普的Akt磷酸化而减弱。DNA损伤后，雅普过表达增加，而雅普缺失减少，p73介导的细胞凋亡以Akt可逆转的方式发生。因此，雅普的Akt磷酸化可抑制细胞损伤后促凋亡基因表达反应的诱导。
We have used an affinity purification method to identify substrates of protein kinase B/Akt. One protein that associates with 14-3-3 in an Akt-dependent manner is shown here to be the Yes-associated protein (YAP), which is phosphorylated by Akt at serine 127, leading to binding to 14-3-3. Akt promotes YAP localization to the cytoplasm, resulting in loss from the nucleus where it functions as a coactivator of transcription factors including p73. p73-mediated induction of Bax expression following DNA damage requires YAP function and is attenuated by Akt phosphorylation of YAP. YAP overexpression increases, while YAP depletion decreases, p73-mediated apoptosis following DNA damage, in an Akt inhibitable manner. Akt phosphorylation of YAP may thus suppress the induction of the proapoptotic gene expression response following cellular damage.