Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR).
2002; National Institutes of Health; Volume: 62; Issue: 8 Linguagem: Inglês
Autores
Abujiang Pataer, Stephan A. Vorburger, Glen N. Barber, Sunil Chada, Abner M. Mhashilkar, Helena Zou-Yang, Alexis Stewart, Siddharth Balachandran, Jack A. Roth, Kelly K. Hunt, Stephen G. Swisher,
Tópico(s)interferon and immune responses
ResumoAdenoviral-mediated overexpression of the melanoma differentiation-associated gene 7 (Ad-mda7) induces apoptosis in a wide range of cancer cells, although themechanism is not well understood. We report that Ad-mda7 induces andactivates the double-stranded RNA-dependent protein kinase (PKR), which leads to phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2alpha) and the induction of apoptosis in lung cancer cells. Treatment with 2-aminopurine (2-AP), a serine/threonine kinase inhibitor, inhibits PKR activation, eIF2alpha phosphorylation, and apoptosis induction by Ad-mda7. Additionally, PKR null but not wild-type fibroblasts are resistant to Ad-mda7-induced apoptosis. These results suggest that the activation of PKR and its downstream targets may be a critical pathway for Ad-mda7-mediated apoptosis.
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