p53 Family and Cellular Stress Responses in Cancer

Abstract

p53 is an important tumor suppressor gene, which is stimulated by cellular stress like ionizing radiation, hypoxia, carcinogens, and oxidative stress. Upon activation, p53 leads to cell-cycle arrest and promotes DNA repair or induces apoptosis via several pathways. p63 and p73 are structural homologs of p53 that can act similarly to the protein and also hold functions distinct from p53. Today more than 40 different isoforms of the p53 family members are known. They result from transcription via different promoters and alternative splicing. Some isoforms have carcinogenic properties and mediate resistance to chemotherapy. Therefore, expression patterns of the p53 family genes can offer prognostic information in several malignant tumors. Furthermore, the p53 family constitutes a potential target for cancer therapy. Small molecules (e.g., Nutlins, RITA, PRIMA-1, and MIRA-1 among others) have been objects of intense research interest in recent years. They restore pro-apoptotic wild-type p53 function and were shown to break chemotherapeutic resistance. Due to p53 family interactions small molecules also influence p63 and p73 activity. Thus, the members of the p53 family are key players in the cellular stress response in cancer and are expected to grow in importance as therapeutic targets.

Expression of Interactive Genes Associated with Apoptosis and Their Prognostic Value for Ovarian Serous Adenocarcinoma

“…3. Assessment of prognostic significance using Kaplan-Meier survival estimates and log-rank test signaling pathways, resulting in tumor cell survival, even though they are under the pathologic condition [12].…”

Major apoptotic mechanisms and genes involved in apoptosis

“…DNAbinding domain binds to response elements of target genes, whereas the N-terminal trans-activation domain forms binding sites for several negative or positive regulators. The Cterminal domain undergoes alternative splicing and posttranslational modifications [137]. p53 acts as tetrameric transcription factor, which controls the expression of a large set of genes involved in significant cellular processes including DNA damage detection, cell cycle arrest, apoptosis, DNA repair, and senescence [134].…”

The anticancer effect of Huaier (Review)

“…The p53 tumor-suppressor gene can influence cell cycle progression, DNA damage repair, genomic stability and thus inhibit the proliferation of cancer cells (22). To determine whether the proliferation inhibitory effect of Huaier is due to p53-induced cell-cycle arrest, cell cycle distribution of Huaiertreated MCF-7, MDA-MB-231 and A875 cells was analyzed by flow cytometry (19,20).…”