Resumen
TP53, the most frequently mutated gene in human cancers, has a key role in the maintenance of the genetic stability and, thus, in preventing tumor development. The p53-dependent responses were long thought to be solely driven by canonical p53a. However, it is now known that TP53 physiologically expresses at least 12 p53 isoforms including ?133p53a, ?133p53ß and ?133p53?. The ?133p53 isoforms are potent modulators of the p53 pathway that regulate critical functions in cancer, physiological and premature aging, neurodegenerative diseases, immunity and inflammation, and tissue repair. This review aims to summarize the current knowledge on the ?133p53 isoforms and how they contribute to multiple physiological and pathological mechanisms. Critically, further characterization of p53 isoforms may identify novel regulatory modes of p53 pathway functions that contribute to disease progression and facilitate the development of new therapeutic strategies.