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dc.contributor.authorMahalingam, D
dc.contributor.authorKeane, M
dc.contributor.authorPirianov, G
dc.contributor.authorMehmet, H
dc.contributor.authorSamali, A
dc.contributor.authorSzegezdi, E
dc.date.accessioned2018-09-20T16:15:31Z
dc.date.available2018-09-20T16:15:31Z
dc.date.issued2009-04-07
dc.identifier.citationMahalingam, D; Keane, M; Pirianov, G; Mehmet, H; Samali, A; Szegezdi, E (2009). Differential activation of jnk1 isoforms by trail receptors modulate apoptosis of colon cancer cell lines. British Journal of Cancer 100 (9), 1415-1424
dc.identifier.issn0007-0920,1532-1827
dc.identifier.urihttp://hdl.handle.net/10379/12580
dc.description.abstractTumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis on binding to its receptors, death receptor 4 and 5 (DR4, DR5). TRAIL can also activate c-Jun N-terminal kinase (JNK) through the adaptor molecules, TNF receptor-associated factor 2 (TRAF2) and receptor-interacting protein (RIP). The role of JNK in TRAIL-induced tumour cell apoptosis is unclear. In this study, we demonstrate that JNK is activated by TRAIL in colon cancer cells. Inhibition of JNK with L-JNKI reduced rhTRAIL-induced cell death but enhanced cell death induced by selective activation of DR4 or DR5. This difference was unrelated to receptor internalisation or differential activation of c-Jun, but activation of different JNK isoforms. Our data demonstrate that JNK1, but not JNK2 is activated by rhTRAIL in the examined colon cancer cell lines. Although rhTRAIL activated both the long and short isoforms of JNK1, selective activation of DR4 or DR5 led to predominant activation of the short JNK1 isoforms (JNK1 alpha 1 and/or JNK1 beta 1). Knockdown of JNK1 alpha 1 by shRNA enhanced apoptosis induced by TRAIL, agonistic DR4 or DR5 antibodies. On the other hand, knockdown of the long JNK1 isoforms (JNK1 alpha 2 and JNK1 beta 2) had the opposite effect; it reduced TRAIL-induced cell death. These data indicate that the short JNK1 isoforms transmit an antiapoptotic signal, whereas the long isoforms (JNK1 alpha 2 or JNK1 beta 2) act in a proapoptotic manner.
dc.publisherSpringer Nature
dc.relation.ispartofBritish Journal of Cancer
dc.subjecttrail
dc.subjectc-jun
dc.subjectjnk1 alpha 1
dc.subjectcolon carcinoma
dc.subjectapoptosis
dc.subjectdr4
dc.subjectdr5
dc.subjectn-terminal kinase
dc.subjectprotein-kinases
dc.subjectbinding protein
dc.subjectkappa-b
dc.subjectdeath
dc.subjectligand
dc.subjectphosphorylation
dc.subjectfibroblasts
dc.subjectinhibitors
dc.subjectpathways
dc.titleDifferential activation of jnk1 isoforms by trail receptors modulate apoptosis of colon cancer cell lines
dc.typeArticle
dc.identifier.doi10.1038/sj.bjc.6605021
dc.local.publishedsourcehttp://www.nature.com/bjc/journal/v100/n9/pdf/6605021a.pdf
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