Dram1 regulates DNA damage-induced alternative autophagy
Dram1 regulates DNA damage-induced alternative autophagy
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DOI：
10.15698/cst2018.03.127
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发表时间：
2018-03-01
期刊：
影响因子：
6.4
通讯作者：
Shimizu, Shigeomi
中科院分区：
文献类型：
--
作者：
Nagata, Meruna;Arakawa, Satoko;Shimizu, Shigeomi
自噬是一种进化保守的降解亚细胞成分的过程。哺乳动物细胞经历两种类型的自噬：Atg5依赖性常规自噬和Atg5独立性替代性自噬，后一种类型的自噬所需的分子在很大程度上是未知的。在本研究中，我们分析了遗传毒性应激诱导的交替性自噬的分子机制，并确定了p53和损伤调节自噬调节因子（Dram1）的重要作用。Dram1足以诱导替代性自噬。在替代性自噬的机制中，Dram1在p53下游的隔离膜的关闭中起作用。这些发现表明Dram1在遗传毒性应激诱导的替代性自噬中起着关键作用。
Autophagy is an evolutionarily conserved process that degrades subcellular constituents. Mammalian cells undergo two types of autophagy; Atg5-dependent conventional autophagy and Atg5-independent alternative autophagy, and the molecules required for the latter type of autophagy are largely unknown. In this study, we analyzed the molecular mechanisms of genotoxic stress-induced alternative autophagy, and identified the essential role of p53 and damage-regulated autophagy modulator (Dram1). Dram1 was sufficient to induce alternative autophagy. In the mechanism of alternative autophagy, Dram1 functions in the closure of isolation membranes downstream of p53. These findings indicate that Dram1 plays a pivotal role in genotoxic stress-induced alternative autophagy.