Interferon-inducible p202 in the susceptibility to systemic lupus

Systemic lupus erythematosus (SLE) is the prototype systemic autoimmune disease, which has potential to involve multiple organ systems. Studies in human SLE patients and murine models of lupus have indicated that genetic predisposition plays a crucial role in the development of this disease. To identify the genetic basis of human lupus and to understand the molecular mechanisms, mouse models of SLE have been studied. Generation of mice congenic for the Nba2 locus on the C57BL/6 genetic background, coupled with gene expression profiling, recently identified the interferon-activatable Ifi202 gene (encodes the protein p202) as a candidate lupus-susceptibility gene. The protein p202 is a member of the 200-protein family. The family includes structurally and functionally related mouse and human interferon-inducible proteins. The protein p202 (52-kDa) is a relatively well-characterized phosphoprotein in the family with demonstrated ability to control cell-signaling pathways regulating cell proliferation, survival, and differentiation. Here, we review what is known about the gene Ifi202 and the protein it encodes. Moreover, we discuss how an understanding of the role of p202 in cell growth regulation, particularly in cells of the immune system, will help elucidate the molecular mechanisms contributing to the development of lupus.