Mitochondrial–nuclear p53 trafficking controls neuronal susceptibility in stroke

Abstract

Stroke 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 impaired functional recovery after stroke. The tumor suppressor protein p53 regulates key cellular processes, including cell cycle arrest, DNA repair, senescence, and apoptosis. Under cellular stress conditions, p53 undergoes post‐translational modifications, which control protein localization, stability, and proapoptotic 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 translocates to the mitochondria and interacts with B‐cell lymphoma‐2 family proteins, 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 at codon 72 of the Tp53 gene that controls p53 mitochondrial localization and cell susceptibility to apoptosis supports 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 susceptibility to cerebral ischemia and its impact on functional outcome of stroke patients.

Recognition of the Possible miRNA-mRNA Controlling Network in Stroke by Bioinformatics Examination

“…The protein that suppresses tumors is p53; it is also known for regulating critical cellular processes, including cell cycle arrest, DNA repair, senescence, and apoptosis. It interacts with B cell lymphoma 2 family proteins, thereby activating a mitochondrial apoptotic program with greater efficiency than its activity as an arrangement factor [ 44 ].…”

Integrative Analyses of Biomarkers Associated with Endoplasmic Reticulum Stress in Ischemic Stroke

“…Previous reports have shown that ERS can induce significant upregulation of TP53 [ 47 ]. Rapid and substantial accumulation of TP53 was observed in the ischemic penumbra, which resulted in neuronal apoptosis [ 48 ]. Therefore, TP53 may be a potential therapeutic target of IS.…”

Cytotoxic and anticancer activity of a novel synthesized tet-AuNPs simultaneously activates p53 and inhibits NF-kB signaling in SKBR3 cell line

“…Along with this, AuNPs treated SKBR3 cells also exhibited marked upregulation of p53 mRNA. This implied that AuNPs successfully stimulated apoptosis induction via p53 through targeted activation of downstream genes in addition to the transactivationindependent route at mitochondria [28]. This was because suppression of cancer proliferation by p53 involves cell growth arrest, so that DNA repair can take place [29], but if DNA insulted by a drug was severe enough then p53 recruited pro-apoptotic members for apoptosis [30].…”