Ligand-independent anti-oncogenic activity of the alpha subunit of the type I interferon receptor

Two interferon (IFN) alpha-regulated genes, IRF1/ISGF2 and PKR/p68 kinase, may function as tumor suppressor genes suggesting that the IFN system may function as a tumor suppressor system. We report that the expression of the alpha subunit of the type I IFN receptor in human K-562 cells had anti-onco...

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Bibliographic Details
Published in:The Journal of biological chemistry 1994-11, Vol.269 (44), p.27275-27279
Main Authors: Colamonici, O R, Porterfield, B, Domanski, P, Handa, R K, Flex, S, Samuel, C E, Pine, R, Diaz, M O
Format: Article
Language:English
Subjects:
Animals
Cell Division
DNA-Binding Proteins - physiology
eIF-2 Kinase
Erythropoiesis
Genes, Tumor Suppressor
In Vitro Techniques
Interferon Regulatory Factor-1
Leukemia, Erythroblastic, Acute - pathology
Mice
Mice, Nude
Phosphoproteins - physiology
Protein-Serine-Threonine Kinases - physiology
Protein-Tyrosine Kinases - metabolism
Proteins - physiology
Receptors, Interferon - chemistry
Receptors, Interferon - physiology
Signal Transduction
Tumor Cells, Cultured
TYK2 Kinase
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Summary:Two interferon (IFN) alpha-regulated genes, IRF1/ISGF2 and PKR/p68 kinase, may function as tumor suppressor genes suggesting that the IFN system may function as a tumor suppressor system. We report that the expression of the alpha subunit of the type I IFN receptor in human K-562 cells had anti-oncogenic effects that include a marked decrease in: (i) cell proliferation rate, (ii) the cell density at which growth arrest normally occurs, and (iii) the tumorigenicity in nude mice. Furthermore, expression of the alpha subunit in K-562 cells induced erythroid differentiation. While most cytokine receptors become activated after binding their corresponding ligands, the overexpression of the alpha subunit has a physiological effect in the absence of its natural ligand, type I IFNs, suggesting a novel function for this type I IFN receptor subunit. The anti-oncogenic effect of the alpha subunit is mediated by a pathway that does not involve two tumor suppressor genes induced by type I IFNs, the transcriptional regulator IFN response factor-1 and the RNA-dependent protein kinase, or the p135tyk2 tyrosine kinase that directly associates and phosphorylates the alpha subunit.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)46980-3