【摘 要】
：
Autophagy is a fundamental adaptive response to amino acid starvation orchestrated by a set of evolutionarily conserved gene products, the autophagy (ATG) p
【机 构】
：
CenterforautophagyResearch,universityofTexasSouthwesternMedicalCenteratDallas,Dallas,TX,USA;Departme
【出 处】
：
The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会
论文部分内容阅读
Autophagy is a fundamental adaptive response to amino acid starvation orchestrated by a set of evolutionarily conserved gene products, the autophagy (ATG) proteins.However, the cellular cues that activate the function of ATG proteins during amino acid starvation remain poorly understood.Here we show that two related stress-responsive kinases, members of the p38 mitogen-activated protein kinase (MAPK) signaling pathway MK2 and MK3, positively regulate starvation-induced autophagy by phosphorylating an essential ATG protein, Beclin 1, at serine 90, and that this phosphorylation site is essential for the tumor suppressor function of Beclin 1.Moreover, MK2/MK3-dependent Beclin 1 phosphorylation (and starvation-induced autophagy) is blocked in vitro and in vivo by Bcl-2, a negative regulator of Beclin 1.Together, these findings reveal MK2/MK3 as crucial stress-responsive kinases that promote autophagy through Beclin 1 S90 phosphorylation, and identify the blockade of MK2/3-dependent Beclin 1 S90 phosphorylation as a mechanism by which Bcl-2 inhibits the autophagy function of Beclin 1.
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