Novel function of cytoplasmic p53 at the interface between mitochondria and the endoplasmic reticulum

Germline mutations in the gene coding for tumor protein p53 (TP53, best known as p53) are associated with the Li-Fraumeni syndrome, a dominant hereditary disorder characterized by an increased predisposition of patients to the development of various tumors relatively early in life. In addition, TP53 is affected by somatic loss-of-function mutations in a large fraction (>50%, according to current estimates) of human cancers all confounded.1 Finally, several other molecular defects causally associated with malignant transformation or tumor progression result in the functional inactivation of the p53 system. As a notable example, multiple neoplasms express increased levels of MDM2 proto-oncogene, E3 ubiquitin protein ligase (MDM2), resulting in an accrued degradation of p53 by the proteasome.2 These observations indicate that the loss of p53 functions favors the establishment and/or progression of various malignancies.