[Frontiers in Bioscience 7, e252-262, May 1, 2002]

INTERFERON-INDUCIBLE p202 IN THE SUSCEPTIBILITY TO SYSTEMIC LUPUS

Divaker Choubey 1 & Brian L. Kotzin 2

1 Department of Radiation Oncology, Stritch School of Medicine, Loyola University Medical Center & Hines VA Hospital, 2160 South First Avenue, Maywood, IL 60153, 2 Department of Medicine and Immunology, University of Colorado Health Sciences Center, Division of Clinical Immunology, 4200 East Ninth Avenue, Denver, CO 80262

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The 200-gene family
4. Regulation of p202 expression
4.1. Expression levels depend on the genetic background of mice
4.2. Transcriptional as well as post-transcriptional regulation
4.3. IFN-independent regulation
5. The protein p202a
6. Role of p202 in cell growth regulation
6.1. How does p202 retard cell proliferation?
6.2. Control of cell survival
6.3. Regulation of differentiation
7. Transcriptional modulation by p202
7.1. Regulation of the E2F family of transcription factors
7.2. Functional interactions with p53
8. Future perspectives
9. Acknowledgement
10. References

1. ABSTRACT

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.