BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells
BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells
复制标题
HepG2 细胞中蛋白酶体抑制诱导的 BAG3 依赖性非典型自噬
DOI：
10.4161/auto.24292
复制
发表时间：
2013-06-01
期刊：
影响因子：
13.3
通讯作者：
Wang, Hua-Qin
中科院分区：
文献类型：
--
作者：
Liu, Bao-Qin;Du, Zhen-Xian;Wang, Hua-Qin
新出现的证据表明，泛素-蛋白酶体系统（UPS）的阻断激活自噬。调节它们之间关系的分子参与者仍有待阐明。BAG 3是BAG辅伴侣蛋白家族的成员之一，它调节热休克蛋白70（HSP 70）伴侣蛋白家族的ATP酶活性。研究表明BAG 3在多种生理和病理过程中发挥作用，包括抗凋亡活性、信号转导、病毒感染的调节作用、细胞粘附和迁移等。近年来，它在自噬启动中的作用引起了人们的广泛关注。目前的研究首次表明，蛋白酶体抑制剂引起非典型的自噬，这是没有抑制III类磷脂酰肌醇3-激酶（PtdIns 3 K）或针对Beclin 1（BECN 1）的shRNA抑制剂。此外，我们证明BAG 3归因于蛋白酶体抑制剂引起的自噬激活，并且MAPK 8/9/10（也分别称为JNK 1/2/3）激活也通过BAG 3的上调而涉及。此外，我们发现，非典型的自噬介导的BAG 3抑制HepG 2细胞的蛋白酶体抑制剂的反应。
Emerging lines of evidence have shown that blockade of ubiquitin-proteasome system (UPS) activates autophagy. The molecular players that regulate the relationship between them remain to be elucidated. Bcl-2 associated athanogene 3 (BAG3) is a member of the BAG co-chaperone family that regulates the ATPase activity of heat shock protein 70 (HSP70) chaperone family. Studies on BAG3 have demonstrated that it plays multiple roles in physiological and pathological processes, including antiapoptotic activity, signal transduction, regulatory role in virus infection, cell adhesion and migration. Recent studies have attracted much attention on its role in initiation of autophagy. The current study, for the first time, demonstrates that proteasome inhibitors elicit noncanonical autophagy, which was not suppressed by inhibitors of class III phosphatidylinositol 3-kinase (PtdIns3K) or shRNA against Beclin 1 (BECN1). In addition, we demonstrate that BAG3 is ascribed to activation of autophagy elicited by proteasome inhibitors and MAPK8/9/10 (also known as JNK1/2/3 respectively) activation is also implicated via upregulation of BAG3. Moreover, we found that noncanonical autophagy mediated by BAG3 suppresses responsiveness of HepG2 cells to proteasome inhibitors.