Details

Autor(en) / Beteiligte

• Colamonici, O R
• Porterfield, B
• Domanski, P
• Handa, R K
• Flex, S
• Samuel, C E
• Pine, R
• Diaz, M O

Titel

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

Ist Teil von

• The Journal of biological chemistry, 1994-11, Vol.269 (44), p.27275-27279

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1994

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.