Macroautophagy/autophagy, an evolutionarily conserved eukaryotic bioprocess, plays an important role in the bulk degradation of intracellular macromolecules, organelles, and invading pathogens. PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3) functions as a key protein in autophagy initiation and progression. The activity of PIK3C3 is tightly regulated by multiple post-translational modifications, including ubiquitination, however, the regulatory mechanisms underpinning the reversible deubiquitination of PIK3C3 remain poorly understood. Recently, we identified the E3 ubiquitin ligase NEDD4/NEDD4-1 as a positive regulator of autophagy through decreasing the K48-linked ubiquitination of PIK3C3 by recruiting USP13.

中文翻译：

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NEDD4-USP13轴通过去泛素化PIK3C3促进自噬。

巨自噬/自噬是一种进化上保守的真核生物过程，在细胞内大分子，细胞器和入侵病原体的整体降解中起重要作用。PIK3C3 / VPS34（磷脂酰肌醇3激酶催化亚基3型）在自噬启动和发展中起关键蛋白的作用。PIK3C3的活性受到多种翻译后修饰（包括泛素化）的严格调控，但是，对PIK3C3可逆去泛素化基础的调控机制仍然知之甚少。最近，我们通过招募USP13来降低E3泛素连接酶NEDD4 / NEDD4-1作为自噬的正调节剂，从而降低了PIK3C3的K48连接泛素化。