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p53 and variants in inflammatory disease and cancer

66 months
Approved budget:
Professor Antony Braithwaite
Health issue:
Cancer (oncology)
Proposal type:
Lay summary
Cancer is the leading cause of death in New Zealand. Thus, better treatments are required. Defects in the p53 tumour suppressor pathway are commonplace in human cancers making it an attractive target for therapies. However, the p53 pathway is complex, made more so by the discovery of 12 p53 variants (isoforms) and novel transcripts. Here we investigate how p53 works and how p53 isoforms and other variants cause cancer. We will investigate the functions and clinical significance of p53 isoforms using a mouse model of the Δ133p53 isoform, clinical material and gene activity databases, which enable us to correlate aberrations in both known and unexplored regions of the p53 gene, with clinical parameters. Similar studies will be done using tissue from patients with autoimmune disease as Δ133p53 mice display inflammatory/autoimmune features. Links between cancer and inflammation will be examined. Understanding the importance of p53 variants will lead to better therapies.