Adaptive homeostasis and the p53 isoform network

Abstract

All living organisms have developed processes to sense and address environmental changes to maintain a stable internal state (homeo- stasis). When activated, the p53 tumour suppressor maintains cell and organ integrity and functions in response to homeostasis disruptors (stresses) such as infection, metabolic alterations and cellular damage. Thus, p53 plays a fundamental physiological role in maintaining organismal homeostasis. The TP53 gene encodes a net- work of proteins (p53 isoforms) with similar and distinct biochemi- cal functions. The p53 network carries out multiple biological activities enabling cooperation between individual cells required for long-term survival of multicellular organisms (animals) in response to an ever-changing environment caused by mutation, infection, metabolic alteration or damage. In this review, we suggest that the p53 network has evolved as an adaptive response to pathogen infec- tions and other environmental selection pressures.