title: Does Δ133p53 isoform trigger inflammation and autoimmunity?
abstract: Autoimmune diseases are characterized by the immune system mounting a response against self. The exact etiology of autoimmune diseases and autoimmunity remain unclear. Here, we demonstrate that Δ133p53, an isoform of the tumor suppressor protein p53, is involved in the development of autoimmunity. We have previously generated a mouse model of Δ133p53 (Δ122p53). Δ122p53 mice develop an autoimmune/ inflammation-like phenotype that includes the production of autoantibodies, elevated levels of pro-inflammatory cytokines and lymphocyte aggregations in various organs. Microarray analysis reveals that expression of Δ122p53 induces a number of pro-inflammatory genes, including the STAT1 pathway and interferon-related transcription profile. Comparative genetic signatures have been observed in human SLE (systemic lupus erythematosus) patients, and we show that Δ133p53 regulates STAT1 in human cells. Our findings provide the first evidence of a role for p53 isoforms in the development of autoimmune disease.
authors.affiliation: Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.
authors.forename: Hamish G
authors.initials: HG
authors.lastname: Campbell
authors.forename: Tania L
authors.initials: TL
authors.lastname: Slatter
authors.forename: Aaron
authors.initials: A
authors.lastname: Jeffs
authors.forename: Reena
authors.initials: R
authors.lastname: Mehta
authors.forename: Carina
authors.initials: C
authors.lastname: Rubio
authors.forename: Margaret
authors.initials: M
authors.lastname: Baird
authors.forename: Antony W
authors.initials: AW
authors.lastname: Braithwaite
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism*; D015551:Autoimmunity / Q000235:genetics; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D020033:Protein Isoforms; D050794:STAT1 Transcription Factor; D016159:Tumor Suppressor Protein p53