PML Is a Primary Target Gene of Interferon and Could Mediate Some of Its Biological Activities

Abstract

Interferons (IFNs) are a family of secreted proteins with antiviral, antiproliferative and immunomodulatory activities. On the basis of their antigenic properties, they are classified as three major groups α, β, and γ. IFNs α and β(type I) are produced by many cell types upon viral infection, double stranded RNA treatment, or other stimuli, whereas IFN γ (type II) is induced in T lymphocytes or natural killer cells in response to antigens or mitogens (Chelbi-Alix et al., 1994; Chelbi-Alix and Chousterman, 1992; Pestka et al., 1987; Sen and Ransohoff, 1993). After interacting with their cognate cell surface receptors, IFNs α/β and IFN γ activate different signal transduction cascades leading to the transcription of distinct sets of genes which mediate the biological effects of these cytokines. The IFN α/β- and the IFN γ-inducible gene promoters are characterized by the presence of consensus elements the interferon-stimulated response element (ISRE) and the gamma activated sequence (GAS) respectively. Binding of both IFN α/β and IFN γ results in the differential activation of latent cytoplasmic transcription factors termed STATS (Signal Transducer and Activator of Transcription) that act at different cis-acting DNA elements. Tyk2 and JAK1 kinases play a central roles in the induction of IFN α/β; responsive genes and JAK1 and JAK2 in that of IFN γ (Pelligrini and Schindler, 1993)