Novel role of c-jun N-terminal kinase in regulating the initiation of cap-dependent translation

  • Authors:
    • Manish R. Patel
    • Ahad A. Sadiq
    • Joe Jay-Dixon
    • Tanawat Jirakulaporn
    • Blake A. Jacobson
    • Faris Farassati
    • Peter B. Bitterman
    • Robert A. Kratzke
  • View Affiliations

  • Published online on: November 4, 2011     https://doi.org/10.3892/ijo.2011.1252
  • Pages: 577-582
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Abstract

Initiation of protein translation by the 5' mRNA cap is a tightly regulated step in cell growth and proliferation. Aberrant activation of cap-dependent translation is a hallmark of many cancers including non-small cell lung cancer. The canonical signaling mechanisms leading to translation initiation include activation of the Akt/mTOR pathway in response to the presence of nutrients and growth factors. We have previously observed that inhibition of c-jun N-terminal kinase (JNK) leads to inactivation of cap-dependent translation in mesothelioma cells. Since JNK is involved in the genesis of non-small cell lung cancer (NSCLC), we hypothesized that JNK could also be involved in activating cap-dependent translation in NSCLC cells and could represent an alternative pathway regulating translation. In a series of NSCLC cell lines, inhibition of JNK using SP600125 resulted in inhibition of 4E-BP1 phosphorylation and a decrease in formation of the cap-dependent translation complex, eIF4F. Furthermore, we show that JNK-mediated inhibition of translation is independent of mTOR. Our data provide evidence that JNK is involved in the regulation of translation and has potential as a therapeutic target in NSCLC.

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February 2012
Volume 40 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Patel, M.R., Sadiq, A.A., Jay-Dixon, J., Jirakulaporn, T., Jacobson, B.A., Farassati, F. ... Kratzke, R.A. (2012). Novel role of c-jun N-terminal kinase in regulating the initiation of cap-dependent translation. International Journal of Oncology, 40, 577-582. https://doi.org/10.3892/ijo.2011.1252
MLA
Patel, M. R., Sadiq, A. A., Jay-Dixon, J., Jirakulaporn, T., Jacobson, B. A., Farassati, F., Bitterman, P. B., Kratzke, R. A."Novel role of c-jun N-terminal kinase in regulating the initiation of cap-dependent translation". International Journal of Oncology 40.2 (2012): 577-582.
Chicago
Patel, M. R., Sadiq, A. A., Jay-Dixon, J., Jirakulaporn, T., Jacobson, B. A., Farassati, F., Bitterman, P. B., Kratzke, R. A."Novel role of c-jun N-terminal kinase in regulating the initiation of cap-dependent translation". International Journal of Oncology 40, no. 2 (2012): 577-582. https://doi.org/10.3892/ijo.2011.1252