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J. Virol. doi:10.1128/JVI.01593-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Novel Characteristics of the Function and Induction of Murine p56 Family Proteins

Department of Molecular Genetics, The Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio

^* To whom correspondence should be addressed. Email: seng{at}ccf.org.

	Abstract

The Interferon-stimulated gene (ISG) 56 family is induced strongly in response to virus infection, interferons (IFN) and double-stranded (ds) RNA. In the mouse, this family comprises three members, ISG56, ISG54 and ISG49, which are clustered on chromosome 19 and encode the corresponding proteins p56, p54 and p49. Here, we report differential properties of these proteins and their distinct induction patterns in different cell types. All three murine proteins bound to the c-subunit of the translation initiation factor eIF3, but unlike the other members, p49 did not inhibit protein synthesis. Using a newly raised antibody, we demonstrated that both in vitro and in vivo, p49 expression was strongly induced by IFN, dsRNA and Sendai virus. However, in kidney mesangial cells, as opposed to podocytes, EMCV, VSV or extracellular dsRNA did not induce any of the p56 family proteins, although they were robustly expressed after Sendai virus infection or dsRNA transfection. Furthermore, protein-specific differences in regulation of p56 family members became evident in various leukocyte types: All three proteins were induced by IFN in T cells, but in B cells p56 and ISG56 mRNA could not be detected. Similarly, p56 was selectively uninducible in plasmacytoid dendritic cells, whereas in myeloid dendritic cells, all three family members were expressed. These results revealed novel cell type-, inducer- and gene-specific regulation of the ISG56 family of genes.