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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
Issue Date
14-3-3 Proteins/metabolism ; Antibodies/pharmacology ; Cell Line, Tumor ; Enzyme Activation/drug effects ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism* ; MAP Kinase Kinase 4/antagonists & inhibitors ; MAP Kinase Kinase 4/genetics ; MAP Kinase Kinase Kinase 1/antagonists & inhibitors ; MAP Kinase Kinase Kinase 1/immunology ; MAP Kinase Kinase Kinase 1/metabolism ; MAP Kinase Kinase Kinase 1/physiology* ; MAP Kinase Kinase Kinase 4/antagonists & inhibitors ; MAP Kinase Kinase Kinase 4/immunology ; MAP Kinase Kinase Kinase 4/metabolism ; MAP Kinase Kinase Kinase 4/physiology* ; Phosphorylation/drug effects ; Protein Binding/drug effects ; Protein Binding/physiology ; RNA, Small Interfering/pharmacology ; TNF-Related Apoptosis-Inducing Ligand/pharmacology* ; p38 Mitogen-Activated Protein Kinases/metabolism*
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. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
Yonsei Authors
Kim, So Young(김소영)
Kim, Joo Hang(김주항)
Sun, Bo Kyung(선보경)
Song, Jae Jin(송재진) ORCID logo https://orcid.org/0000-0001-8183-9550
Oh, Se Eun(오세은)
Nguyen, Hoan N.(응구엔응옥호안)
Choi, Hye Jin(최혜진) ORCID logo https://orcid.org/0000-0001-5917-1400
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