A mouse model of the Δ133p53 isoform: roles in cancer progression and inflammation
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This review paper outlines studies on the Δ122p53 mouse, a model of the human Δ133p53 isoform, together with studies in other model organisms, cell culture, and where available, clinical investigations. In general, these studies imply that, in contrast to the canonical p53 tumor suppressor, Δ133p53 family members have oncogenic capability. Δ122p53 is multi-functional, conferring survival and proliferative advantages on cells, promoting invasion, metastasis and vascularization, as does Δ133p53. Cancers with high levels of Δ133p53 often have poor prognosis. Δ122p53 mediates its effects through the JAK–STAT and RhoA–ROCK signaling pathways. We propose that Δ133p53 isoforms have evolved as inflammatory signaling molecules to deal with the consequent tissue damage of p53 activation. However, if sustained expression of the isoforms occur, pathologies may result.
We thank Kim Parker for critically reading the manuscript. We also acknowledge financial support from the Health Research Council of NZ, the Royal Society of NZ Marsden Fund, James Cook Fellowship to AWB, and the Cancer Institute NSW.
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Conflict of interest
The authors declare no potential conflicts of interest.
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