PMID- 35306025
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20220429
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 414
IP  - 2
DP  - 2022 May 15
TI  - JNK initiates Beclin-1 dependent autophagic cell death against Akt activation.
PG  - 113105
LID - S0014-4827(22)00098-2 [pii]
LID - 10.1016/j.yexcr.2022.113105 [doi]
AB  - 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.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Zeng, Chao
AU  - Zeng C
AD  - Department of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu, 
      610031, PR China. Electronic address: chaozeng0106@163.com.
FAU - Zhang, Zhixuan
AU  - Zhang Z
AD  - 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. Electronic address: zxuanzhang0106@126.com.
FAU - Luo, Wei
AU  - Luo W
AD  - 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. Electronic address: weiluo0106@yeah.net.
FAU - Wang, Liyang
AU  - Wang L
AD  - 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. Electronic address: amyloidtau@126.com.
FAU - Zhou, Hang
AU  - Zhou H
AD  - 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. Electronic address: hangzhoutau@163.com.
FAU - Nie, Chunlai
AU  - Nie C
AD  - Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan 
      University, 17# People's South Road, Chengdu, 610041, PR China. Electronic 
      address: niecl1022@scu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220317
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Beclin-1)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - 14-3-3 Proteins/metabolism
MH  - Apoptosis
MH  - *Autophagic Cell Death
MH  - Autophagy/physiology
MH  - Beclin-1/genetics/metabolism
MH  - Cell Line, Tumor
MH  - *Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - bcl-2-Associated X Protein/genetics/metabolism
OTO - NOTNLM
OT  - ABT-199
OT  - Akt
OT  - Autophagy
OT  - Beclin-1
OT  - Cell death
OT  - JNK
EDAT- 2022/03/21 06:00
MHDA- 2022/04/30 06:00
CRDT- 2022/03/20 20:27
PHST- 2022/01/06 00:00 [received]
PHST- 2022/03/07 00:00 [revised]
PHST- 2022/03/10 00:00 [accepted]
PHST- 2022/03/21 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2022/03/20 20:27 [entrez]
AID - S0014-4827(22)00098-2 [pii]
AID - 10.1016/j.yexcr.2022.113105 [doi]
PST - ppublish
SO  - Exp Cell Res. 2022 May 15;414(2):113105. doi: 10.1016/j.yexcr.2022.113105. Epub 
      2022 Mar 17.