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

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A E Koromilas1, S Roy, G N Barber

  • 1Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Canada.

Science (New York, N.Y.)
|September 18, 1992
PubMed

Insights

The double-stranded RNA-dependent protein kinase (dsRNA-PK) mediates interferon effects by regulating protein synthesis. Its loss of function can lead to malignant cell transformation, suggesting it acts as a tumor suppressor.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • The double-stranded RNA-dependent protein kinase (dsRNA-PK) is a crucial mediator of antiviral and antiproliferative responses induced by interferons (IFNs).
  • Physiological studies indicate dsRNA-PK's role in regulating protein synthesis, impacting cell growth and differentiation.

Purpose of the Study:

  • To investigate the physiological function of dsRNA-PK in cell growth and protein synthesis.
  • To determine the role of dsRNA-PK in tumorigenesis and cell proliferation.

Main Methods:

  • In vitro and in vivo studies involving autophosphorylation and activation of dsRNA-PK.
  • Analysis of eIF-2 alpha subunit phosphorylation and protein synthesis inhibition.
  • Expression of a functionally defective human dsRNA-PK mutant in NIH 3T3 cells.

Main Results:

  • Autophosphorylation and activation of dsRNA-PK lead to eIF-2 alpha subunit phosphorylation and inhibition of protein synthesis.
  • Expression of a defective dsRNA-PK mutant in NIH 3T3 cells resulted in malignant transformation.

Conclusions:

  • dsRNA-PK plays a significant role in regulating protein synthesis, cell growth, and differentiation.
  • dsRNA-PK functions as a suppressor of cell proliferation and tumorigenesis, as evidenced by malignant transformation upon its functional defect.

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