SI – CROSSTALK: Mitochondrial‐nuclear p53 trafficking controls neuronal susceptibility in stroke

SUMMARYStroke is a major cause of death and long ‐term disability in the adult. Neuronal apoptosis plays an essential role in the pathophysiology of ischemic brain damage and the impaired functional recovery after stroke. The tumor suppressor protein p53 regulates key cellular processes, including cell cycle arrest, DNA repair, senescence, and a poptosis. Under cellular stress conditions, p53 undergoes post‐translational modifications, which controls protein localization, stability, and pro‐apoptotic activity. After stroke, p53 rapidly accumulates in the ischemic brain, where it activates neuronal apoptosis, through both transcriptional dependent and independent programs. Over the last years, subcellular localization of p53 has emerged as an important regulator of ischemia‐induced neuronal apoptosis. Upon an ischemic insult, p53 rapidly translocate to the mitochondria and interacts with BCL‐2 (B‐cell lymphoma‐2) family pro teins, which activate the mitochondrial apoptotic program, with higher efficacy than through its activity as a transcription factor. Moreover, the identification of a human single nucleotide polymorphism (SNP) at codon 72 of theTp53 gene that controls p53 mitochondrial localization and cell susceptibility to apoptosis support the important role of the p53 mitochondrial program in neuronal survival and functional recovery after stroke. In this article, we review the relevance of mitochondrial and nuclear localization of p53 on neuronal suscepti...
Source: IUBMB Life - Category: Research Authors: Tags: CRITICAL REVIEW Source Type: research