Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase

Antonis E. Koromilas, Sophie Roy, Glen N. Barber, Michael G. Katze, Nahum Sonenberg

Research output: Contribution to journalArticle

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Abstract

The double-stranded RNA-dependent protein kinase (dsRNA-PK) is thought to be a key mediator of the antiviral and antiproliferative effects of interferons (IFNs). Studies examining the physiological function of the kinase suggest that it participates in cell growth and differentiation by regulating protein synthesis. Autophosphorylation and consequent activation of dsRNA-PK in vitro and in vivo result in phosphorylation of the α subunit of eukaryotic initiation factor-2 (eIF-2) and inhibition of protein synthesis. Expression of a functionally defective mutant of human dsRNA-PK in NIH 3T3 cells resulted in malignant transformation, suggesting that dsRNA-PK may function as a suppressor of cell proliferation and tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1685-1689
Number of pages5
JournalScience
Volume257
Issue number5077
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • General

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