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MEKK1/MEKK4 are responsible for TRAIL-induced JNK/p38 phosphorylation

 Bo K Sun  ;  Joo-Hang Kim  ;  Hoan N. Nguyen  ;  Seeun Oh  ;  So Y. Kim  ;  Hye J.  ;  Hye J. Choi  ;  Yong J. Lee  ;  Jae J. Song 
 Oncology Reports, Vol.25(2) : 537-544, 2011 
Journal Title
 Oncology Reports 
Issue Date
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to activate mitogen-activated protein kinases (MAPKs) depending on caspase and mammalian sterile 20-like kinase 1 activations. However, the upstream molecule of MAPKs has not yet been identified. The mitogen-activated protein kinase kinase 1 (MEKK1) and the apoptosis signal-regulating kinase 1 (ASK1) are considered to be possible candidates for the action of MAPKKKs induced by TRAIL and the possibility of reactive oxygen species involvement has also been investigated. We found that MEKK1/MEKK4 as opposed to ASK1, are responsible for TRAIL-induced c-Jun NH2-terminal kinase (JNK) or p38 activation, and that their catalytic activity is repressed by the caspase-8 inhibitor, suggesting that the caspase-8 activation induced by TRAIL is indispensible for MEKK activation. The 14-3-3 θ was also shown to interact with and to dissociate from MEKK1 by TRAIL treatment, thus implicating the 14-3-3 protein as a negative regulator of MEKK1 activation. Taken together, we show herein that the upstream molecule of the TRAIL-induced MAPK activation is MEKK, as opposed to ASK1, via the mediation of its signal through JNK/p38 in a caspase-8-dependent manner.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Institute for Cancer Research (암연구소)
Yonsei Authors
김소영(Kim, So Young)
김주항(Kim, Joo Hang)
선보경(Sun, Bo Kyung)
송재진(Song, Jae Jin) ORCID logo https://orcid.org/0000-0001-8183-9550
오세은(Oh, Se Eun)
응구엔응옥호안(Nguyen, Hoan N.)
최혜진(Choi, Hye Jin) ORCID logo https://orcid.org/0000-0001-5917-1400
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