We investigate a role for oncoprotein p53 variants, especially 133p53, in the development of autoimmune disease. The work is based on our transgenic mouse expressing an analogue of 133p53 (designated 122p53), which develops features of autoimmune disease by modulation of pro-inflammatory genes. We will characterise inflammatory pathologies of the mice and investigate a role for the cytokine IL-6 and the STAT-1/interferon pathway as 'driving' autoimmune disease, using 122p53 mice that lack the IL-6 or STAT-1 genes. To translate these findings to humans, we will analyse rheumatoid arthritis (RA) joint tissue for 133p53 expression, relate that to pathology and inflammatory gene transcripts, and quantitate the levels of other p53 isoforms and novel variants to determine if they are associated with inflammatory disease. We will interrogate publicly available RA transcript databases for similar associations using bioinformatics. The outcome of our experiments will be to define the role p53 isoforms play in autoimmune disease.