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

Manish R. Patel, Ahad A. Sadiq, Joe Jay-Dixon, Tanawat Jirakulaporn, Blake A. Jacobson, Faris Farassati, Peter B. Bitterman, Robert A. Kratzke

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)577-582
Number of pages6
JournalInternational Journal of Oncology
Volume40
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • 4E-BP1
  • Cap-dependent translation
  • Non-small cell lung cancer
  • c-jun N-terminal kinase
  • eIF4E

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