title: Novel role of c-jun N-terminal kinase in regulating the initiation of             cap-dependent translation.
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.
authors.affiliation: University of Minnesota Medical School, Division of Hematology, Oncology, and Transplantation, Minneapolis, MN 55455, USA.
authors.forename: Manish R
authors.initials: MR
authors.lastname: Patel
authors.forename: Ahad A
authors.initials: AA
authors.lastname: Sadiq
authors.forename: Joe
authors.initials: J
authors.lastname: Jay-Dixon
authors.forename: Tanawat
authors.initials: T
authors.lastname: Jirakulaporn
authors.forename: Blake A
authors.initials: BA
authors.lastname: Jacobson
authors.forename: Faris
authors.initials: F
authors.lastname: Farassati
authors.forename: Peter B
authors.initials: PB
authors.lastname: Bitterman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000235:genetics* / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000873:Anthracenes; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C411571:EIF4ENIF1 protein, human; C113920:EIF4G1 protein, human; D039603:Eukaryotic Initiation Factor-4G; D029543:Nucleocytoplasmic Transport Proteins; D010750:Phosphoproteins; D012315:RNA Caps; C432165:pyrazolanthrone; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020123:Sirolimus
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