Different requirements for the cytostatic and apoptotic effects of type I interferons. Induction of apoptosis requires ARF but not p53 in osteosarcoma cell lines

Raudel Sandoval, Jiaping Xue, Mark Pilkinton, Debra Salvi, Hiroaki Kiyokawa, Oscar R. Colamonici*

*Corresponding author for this work

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

The regulation of cell growth is one of the most important effects of type I interferons (IFNs). This response may involve a cytostatic effect or the induction of apoptosis depending on the cell context. Often the growth-inhibitory response of type I IFNs is studied in tumor cell lines carrying mutations of tumor suppressor genes, and therefore, the growth-inhibitory effect can be influenced by inactivation of these important regulators of cell proliferation. In this report, we explored the role of the ARF-p53 pathway in the growth-inhibitory effect of type I IFNs. We found that p53 is only induced in cells that express p14ARF (p19ARF in mouse cells). Surprisingly, mouse embryonal fibroblasts that are null for p19ARF or P53, even after transformation with oncogenic RAS, respond as well as wild type to the growth-inhibitory effect of type I IFNs. Similarly, human ARF-/- U2OS and P53-/- SAOS-2 cells show a significant decrease in cell proliferation. However, only SAOS-2 or U2OS reconstituted with inducible p14ARF undergo apoptosis in response to IFNβ treatment, and this effect was not inhibited by expression of dominant negative p53. These data suggest that (i) at least in specific cell types, the induction of apoptosis by type I IFNs requires an ARF pathway that is p53-independent and (ii) the cytostatic and pro-apoptotic effects of type I IFNs employ different pathways.

Original languageEnglish (US)
Pages (from-to)32275-32280
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number31
DOIs
StatePublished - Jul 30 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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