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

Title
TRAIL/MEKK4/p38/HSP27/Akt survival network is biphasically modulated by the Src/CIN85/c-Cbl complex
Authors
Jina Kim;Dongxu Kang;Jae J. Song;Joo-Hang Kim;Bo K. Sun
Issue Date
2013
Journal Title
Cellular Signalling
ISSN
0898-6568
Citation
Cellular Signalling, Vol.25(1) : 372~379, 2013
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.
URI
http://www.sciencedirect.com/science/article/pii/S0898656812002902

http://ir.ymlib.yonsei.ac.kr/handle/22282913/86138
DOI
10.1016/j.cellsig.2012.10.010
Appears in Collections:
1. 연구논문 > 5. Research Institutes > Institute for Cancer Research
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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