VCP/p97 调节 PtdIns3P 的产生和自噬起始。
VCP/p97 modulates PtdIns3P production and autophagy initiation.
机构信息
Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
出版信息
Autophagy. 2021 Apr;17(4):1052-1053. doi: 10.1080/15548627.2021.1898742. Epub 2021 Mar 9.
VCP/p97 is an essential multifunctional protein implicated in a plethora of intracellular quality control systems, and abnormal function of VCP is the underlying cause of several neurodegenerative disorders. We reported that VCP regulates the levels of the macroautophagy/autophagy-inducing lipid phosphatidylinositol-3-phosphate (PtdIns3P) by modulating the activity of the BECN1 (beclin 1)-containing phosphatidylinositol 3-kinase (PtdIns3K) complex. VCP stimulates the deubiquitinase activity of ATXN3 (ataxin 3) to stabilize BECN1 protein levels and also interacts with and promotes the assembly and kinase activity of the PtdIns3K complex. Acute inhibition of VCP activity impairs autophagy induction, demonstrated by a diminished PtdIns3P production and decreased recruitment of early autophagy markers WIPI2 and ATG16L1. Thus, VCP promotes autophagosome biogenesis, in addition to its previously described role in autophagosome maturation.
VCP/p97 是一种重要的多功能蛋白，参与了众多细胞内质量控制系统，而 VCP 的异常功能是几种神经退行性疾病的根本原因。我们曾报道 VCP 通过调节 BECN1（自噬相关蛋白 1）含有的磷脂酰肌醇 3-激酶（PI3K）复合物的活性来调节巨自噬/自噬诱导脂质磷脂酰肌醇-3-磷酸（PtdIns3P）的水平。VCP 刺激 ATXN3（共济失调蛋白 3）的去泛素化酶活性，稳定 BECN1 蛋白水平，同时与 PtdIns3K 复合物相互作用并促进其组装和激酶活性。VCP 活性的急性抑制会损害自噬的诱导，表现在 PtdIns3P 的产生减少和早期自噬标记物 WIPI2 和 ATG16L1 的募集减少。因此，VCP 促进自噬体的生物发生，除了其先前描述的自噬体成熟作用。
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