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

  • Authors:
    • Bo K. Sun
    • Joo-Hang Kim
    • Hoan N. Nguyen
    • Seeun Oh
    • So Y. Kim
    • Sujin Choi
    • Hye J. Choi
    • Yong J. Lee
    • Jae J. Song
  • View Affiliations

  • Published online on: December 7, 2010     https://doi.org/10.3892/or.2010.1079
  • Pages: 537-544
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Abstract

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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February 2011
Volume 25 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Sun BK, Kim J, Nguyen HN, Oh S, Kim SY, Choi S, Choi HJ, Lee YJ and Song JJ: MEKK1/MEKK4 are responsible for TRAIL-induced JNK/p38 phosphorylation. Oncol Rep 25: 537-544, 2011
APA
Sun, B.K., Kim, J., Nguyen, H.N., Oh, S., Kim, S.Y., Choi, S. ... Song, J.J. (2011). MEKK1/MEKK4 are responsible for TRAIL-induced JNK/p38 phosphorylation. Oncology Reports, 25, 537-544. https://doi.org/10.3892/or.2010.1079
MLA
Sun, B. K., Kim, J., Nguyen, H. N., Oh, S., Kim, S. Y., Choi, S., Choi, H. J., Lee, Y. J., Song, J. J."MEKK1/MEKK4 are responsible for TRAIL-induced JNK/p38 phosphorylation". Oncology Reports 25.2 (2011): 537-544.
Chicago
Sun, B. K., Kim, J., Nguyen, H. N., Oh, S., Kim, S. Y., Choi, S., Choi, H. J., Lee, Y. J., Song, J. J."MEKK1/MEKK4 are responsible for TRAIL-induced JNK/p38 phosphorylation". Oncology Reports 25, no. 2 (2011): 537-544. https://doi.org/10.3892/or.2010.1079