2017年9月13日 · As the Atg4 activity is essential and highly specific to autophagy, Atg4 is a prospective target for developing autophagy-specific inhibitors. In this review article, we summarize our current...

LC3/Atg8 的 C 端被 Atg4 蛋白酶酶切后生成细胞质 LC3-I。LC3-I 与磷脂酰乙醇胺 （PE） 也以泛素样反应的方式连接，这个反应需要 Atg7 和 Atg3 （分别为 E1 和 E2 样酶）。LC3 的脂质形式，即 LC3-II，吸附在自噬体膜上。从而将 LC3 与自噬小泡联系起来。

自噬（autophagy=self-eating）意为自体吞噬，是真核细胞在自噬相关基因（autophagy related gene，Atg）的调控下利用溶酶体降解自身细胞质蛋白和受损细胞器的过程。 自噬可防止细胞损伤，促进细胞在营养缺乏的情况下存活，并对细胞毒性刺激作出反应。 自噬包括生理条件下的基础型自噬和应激条件下的诱导型自噬。 前者是细胞的自我保护机制，有益于细胞的生长发育，保护细胞防止代谢应激和氧化损伤，对维持细胞内稳态以及细胞产物的合成、降解和循环再利用具有重 …

Atg5-Atg12-Atg16L复合物 具有类E3连接酶活性, 主要通过激活Atg3酶活性, 促进LC3（也就是Atg8）从Atg3转移到底物磷脂酰乙醇胺(PE)上。一旦自噬体形成后，Atg5-Atg12-Atg16L复合物就从膜上解离下来。

LC3-I 也是通过一个需要 Atg7 和 Atg3（分别对应 E1 和 E2 样酶）参与的泛素样反应，结合到磷脂酰乙醇胺 (PE)。 脂质化形式的 LC3，也称作 LC3-II，附着到自噬体的膜上。

Atg4 cleaves pro-Atg8 to form Atg8-I, exposing a key glycine residue at the C terminus. This step is referred to as “priming” and allows for the conjugation of Atg8 to phosphatidylethanolamine (PE) in the phagophore membrane to produce lipidated Atg8 (Atg8-II), a step necessary for expansion and closure of the membrane [7–11].

2016年4月1日 · Atg4 proteases are cysteine proteases, which are well known for their crucial roles in the lipidation and delipidation of LC3 during the autophagy process. At least four human Atg4 homologs have been reported according to their sequence homology to the yeast Saccharomyces cerevisiae (Sc) Atg4.

Atg8 is constitutively cleaved by Atg4 and upon autophagosome biogenesis induction, it is conjugated to the phosphatidylethanolamine (PE) present in autophagosomal membranes. The Atg8-PE conjugate mediates cargo selection and contributes to …

2017年8月18日 · It has been shown that Atg4 constitutively deconjugates Atg8 from PE on all membranes except the PAS, suggesting the existence of regulatory elements protecting Atg8–PE from cleavage by...

As the Atg4 activity is essential and highly specific to autophagy, Atg4 is a prospective target for developing autophagy-specific inhibitors. In this review article, we summarize our current knowledge of the structure, function and regulation of Atg4 including efforts to develop Atg4-specific inhibitors.