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JNK initiates Beclin-1 dependent autophagic cell death against Akt activation.

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收录情况： ◇ SCIE

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机构： [1]Department of Gastroenterology, The Third People’s Hospital of Chengdu, Chengdu, 610031, PR China [2]Department of Chemotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, PR China [3]Department of Pharmacy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, PR China [4]Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 17# People’s South Road, Chengdu, 610041, PR China

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ABT-199, a specific inhibitor of the Bcl-2 protein, is widely used in clinical trials for hematological tumors and rarely applied to the research of solid tumors. In this study, we used Bax/Bak double knockout (KO) and knockdown (KD) cells as the model and found that ABT-199 initiated autophagic cell death independent of Bax and Bak. ABT-199 initiated Beclin-1-dependent autophagy, which led to cell death. Furthermore, inactivated Akt released Beclin-1 from the 14-3-3 protein through a change in the phosphorylation state of Beclin-1 in ABT-199-treated cells. Moreover, JNK antagonized the function of Akt in Beclin-1-mediated autophagy by phosphorylating the 14-3-3 protein. Phosphorylated 14-3-3 exhibited a decreased interaction with Beclin-1. Therefore, ABT-199 activated the JNK-Akt-14-3-3 signaling pathway to mediate the Beclin-1-dependent autophagic death of Bax/Bak KO and KD cells. These findings may extend the therapeutic application of ABT-199 to colon cancer, particularly apoptosis-deficient tumors.Copyright © 2022. Published by Elsevier Inc.

基金：

基金编号： 81773188 2019YFS0110 320.6750.19094–54

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出版当年[2022]版：

大类 | 3 区医学

小类 | 4 区肿瘤学 4 区细胞生物学

最新[2023]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学 4 区肿瘤学

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出版当年[2022]版：

Q2 ONCOLOGY Q3 CELL BIOLOGY

最新[2023]版：

Q2 ONCOLOGY Q3 CELL BIOLOGY

影响因子： 3.3 最新[2023版] 3.3 最新五年平均 3.7 出版当年[2022版] 3.8 出版当年五年平均 4.145 出版前一年[2021版] 3.3 出版后一年[2023版]

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第一作者机构： [1]Department of Gastroenterology, The Third People’s Hospital of Chengdu, Chengdu, 610031, PR China

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通讯作者：

通讯机构： [4]Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 17# People’s South Road, Chengdu, 610041, PR China [*1]Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 17# People’s South Road, Chengdu, Sichuan Province, 610041, China

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