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TRAIL/MEKK4/p38/HSP27/Akt survival network is biphasically modulated by the Src/CIN85/c-Cbl complex

Authors
 Jina Kim  ;  Dongxu Kang  ;  Bo K. Sun  ;  Joo-Hang Kim  ;  Jae J. Song 
Citation
 CELLULAR SIGNALLING, Vol.25(1) : 372-379, 2013 
Journal Title
 CELLULAR SIGNALLING 
ISSN
 0898-6568 
Issue Date
2013
MeSH
Adaptor Proteins, Signal Transducing/antagonists & inhibitors ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism* ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects* ; Cell Line, Tumor ; Curcumin/pharmacology ; HSP27 Heat-Shock Proteins/metabolism* ; Humans ; MAP Kinase Kinase Kinase 4/metabolism* ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism* ; Proto-Oncogene Proteins c-cbl/antagonists & inhibitors ; Proto-Oncogene Proteins c-cbl/genetics ; Proto-Oncogene Proteins c-cbl/metabolism* ; RNA Interference ; RNA, Small Interfering/metabolism ; Signal Transduction/drug effects ; TNF-Related Apoptosis-Inducing Ligand/pharmacology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; src-Family Kinases/metabolism*
Keywords
CIN85 ; c-Cbl ; MEKK4 ; p38 ; HSP27 ; Src ; TRAIL
Abstract
Previously, we showed that mitogen-activated protein kinase/extracellular signal-related kinase 4 (MEKK4) is responsible for p38 activation and that its activation during tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment also increases the catalytic activity of Akt. Here, we further investigated how the TRAIL-induced MEKK4/p38/heat shock protein (HSP27)/Akt survival network is modulated by the Src/c-Cbl interacting protein of 85 kDa (CIN85)/c-Cbl complex. TRAIL-induced activation of Akt catalytic activity and phosphorylation were highly correlated with p38/HSP27 phosphorylation, whereas the phosphorylation of p38/HSP27 increased further during incubation with curcumin and TRAIL, which caused significant apoptotic cell death. CIN85, a c-Cbl-binding protein, plays an essential role in connecting cell survival to cell death. The interaction of CIN85 with MEKK4 was increased during the late phase of TRAIL incubation, suggesting that sustained p38 and HSP27 phosphorylation protects cells by preventing further cell death. However, further increases in p38/HSP27 phosphorylation induced by cotreatment with curcumin and TRAIL converted cell fate to death. Taken together, these data demonstrate that phosphorylated p38/HSP27 as biphasic modulators act in conjunction with CIN85 to determine whether cells survive or die in response to apoptotic stress.
Full Text
http://www.sciencedirect.com/science/article/pii/S0898656812002902
DOI
10.1016/j.cellsig.2012.10.010
Appears in Collections:
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Hang(김주항)
Song, Jae Jin(송재진) ORCID logo https://orcid.org/0000-0001-8183-9550
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86138
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