p53Ψ is a transcriptionally inactive p53 isoform able to reprogram cells toward a metastatic-like state

• DOI: 10.1073/pnas.1321640111
• Publication Date: 2014-07-30T04:48:59Z
• Authors: Serif Senturk; Zhan Yao; Matthew Camiolo; Brendon Stiles; Trushar Rathod; Alice M. Walsh; Alice Nemajerova; Matthew J. Lazzara; Nasser K. Altorki; Adrian Krainer; Ute M. Moll; Scott W. Lowe; Luca Cartegni; Raffaella Sordella
• Keywords: 0301 basic medicine; Epithelial-Mesenchymal Transition; Lung Neoplasms; CD24 Antigen; Lung Injury; Cadherins; Genes, p53; Introns; Mitochondria; Alternative Splicing; Cyclophilins; Mice; 03 medical and health sciences; Hyaluronan Receptors; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Mutation; Animals; Peptidyl-Prolyl Isomerase F; Humans; Protein Isoforms; Neoplasm Metastasis

Significance p53 is one of the most intensively studied tumor-suppressor genes. We identified a naturally occurring p53 isoform, generated by an alternative-splicing event, that, although lacking transcriptional activity and canonical tumor suppressor functions, is able to reprogram cells toward the acquisition of metastatic features via a cyclophilin D interaction in the mitochondria matrix. Interestingly, this isoform is expressed on tissue injury and in tumors characterized by increased metastatic spread. In some of these tumors, p53-like isoforms are generated by intron 6 mutations. This suggests a possible physiological origin of certain p53 mutations and indicates that mutations resulting in the generation of truncated p53Ψ-like proteins do more than create a 53-null state.