title: Systemic lupus erythematosus and increased risk to develop B cell malignancies: role of the p200-family proteins.
abstract: Systemic lupus erythematosus (SLE), an autoimmune disease, develops at a female-to-male ratio of 10:1. Increased serum levels of type I interferons (IFN-alpha/beta) and induction of "IFN-signature" genes are associated with an active SLE disease in patients. Moreover, SLE patients exhibit three- to four-fold increase in the risk of developing malignancies involving B cells, including non-Hodgkin lymphoma (NHL) and Hodgkin's lymphoma (HL). Interestingly, homozygous mice expressing a deletion mutant (the proline-rich domain deleted) of the p53 develop various types of spontaneous tumors, particularly of B cell origin upon aging. The deletion is associated with defects in transcriptional activation of genes by p53 and inhibition of DNA damage-induced apoptosis. Notably, increased levels of the p202 protein, which is encoded by the p53-repressible interferon-inducible Ifi202 gene, in B cells of female mice are associated with defects in B cell apoptosis, inhibition of the p53-mediated transcription of pro-apoptotic genes, and increased lupus susceptibility. In this review we discuss how increased levels of the p202 protein (and its human functional homologue IFI16 protein) in B cells increase lupus susceptibility and are likely to increase the risk of developing certain B cell malignancies. A complete understanding of the molecular mechanisms that regulate B cell homeostasis is necessary to identify SLE patients with an increased risk to develop B cell malignancies.
authors.affiliation: Department of Environmental Health, University of Cincinnati, 3223 Eden Avenue, PO Box 670056, Cincinnati, OH 45267, United States.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Veeranki
authors.forename: Divaker
authors.initials: D
authors.lastname: Choubey
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012306:Risk; D012737:Sex Factors; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism
chemical_list: C092537:Ifi202b protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53; C076700:IFI16 protein, human