Involvement of phosphorylation of ULK1 in alternative autophagy
Involvement of phosphorylation of ULK1 in alternative autophagy
复制标题
ULK1 磷酸化参与替代自噬
DOI：
10.1080/15548627.2020.1776476
复制
发表时间：
2020
期刊：
影响因子：
13.3
通讯作者：
Shimizu Shigeomi
中科院分区：
文献类型：
--
作者：
Torii Satoru;Shimizu Shigeomi
替代性自噬是一种不依赖于ATG 5（自噬相关5）的、高尔基体膜衍生形式的大自噬。ULK 1（unc-51 like kinase 1）不仅是典型自噬的重要起始因子，也是替代性自噬的重要起始因子。然而，ULK 1如何差异调节两种类型的自噬的机制仍不清楚。最近，我们在Ser 746处发现了ULK 1的一个新的磷酸化位点，这是替代性自噬所需的，但不是典型的自噬。我们还确定RIPK 3（受体相互作用丝氨酸-苏氨酸激酶3）作为负责遗传毒性应激诱导的ULK 1 S746磷酸化的激酶。这些发现表明RIPK 3依赖性ULK 1 S746磷酸化在遗传毒性应激诱导的替代性自噬中起关键作用。
Alternative autophagy is an ATG5 (autophagy related 5)-independent, Golgi membrane-derived form of macroautophagy. ULK1 (unc-51 like kinase 1) is an essential initiator not only for canonical autophagy but also for alternative autophagy. However, the mechanism as to how ULK1 differentially regulates both types of autophagy has remained unclear. Recently, we identified a novel phosphorylation site of ULK1 at Ser746, which is required for alternative autophagy, but not canonical autophagy. We also identify RIPK3 (receptor-interacting serine-threonine kinase 3) as the kinase responsible for genotoxic stress-induced ULK1 S746 phosphorylation. These findings indicate that RIPK3-dependent ULK1 S746 phosphorylation plays a pivotal role in genotoxic stress-induced alternative autophagy.