Tumor protein p53 (TP53) mediates DNA repair and cell proliferation in growing cells. The TP53 gene is a tumor suppressor that regulates the expression of target genes in response to multiple cellular stress factors. ...Tumor protein p53 (TP53) mediates DNA repair and cell proliferation in growing cells. The TP53 gene is a tumor suppressor that regulates the expression of target genes in response to multiple cellular stress factors. Key target genes are involved in crucial cellular events such as DNA repair, cell cycle regulation, apoptosis, metabolism, and senescence. TP53 genetic variants and the activity of the wild-type p53 protein (WT-p53) have been linked to a wide range of tumorigenesis. Various genetic and epigenetic alterations, including germline and somatic mutations, loss of heterozygosity, and DNA methylation, can alter TP53 activity, potentially resulting in cancer initiation and progression. This study was designed to screen three reported mutations in the DNA-binding domain of the p53 protein in breast cancer, to evaluate the relative susceptibility and risk associated with breast cancer in the local population. Genomic DNA was isolated from 30 breast tumor tissues along with controls. Tetra and Tri ARMS PCR were performed to detect mutations in the TP53 coding region. For SNPs c.637C>T and c.733C>T, all analyzed cases were homozygous for the wild-type allele ‘C,’ while for SNP c.745A>G, all cases were homozygous for the wild-type allele ‘A.’ These results indicate no relevance of these three SNPs to cancer progression in our study cohort. Additionally, the findings from whole exon sequencing will help to predict more precise outcomes and assess the importance of TP53 gene mutations in breast cancer patients.展开更多
TP53 is a tumor suppressor gene that is mutated in most cancer types and has been extensively studied in cancer research.p53 plays a critical role in regulating the expression of target genes and is involved in key pr...TP53 is a tumor suppressor gene that is mutated in most cancer types and has been extensively studied in cancer research.p53 plays a critical role in regulating the expression of target genes and is involved in key processes such as apoptosis,cell cycle regulation,and genomic stability,earning it the title“guardian of the genome.”Numerous studies have demonstrated p53’s influence on and regulation of autophagy,ferroptosis,the tumor microenvironment,and cell metabolism,all of which contribute to tumor suppression.Alterations in p53,specifically mutant p53(mutp53),not only impair its tumor-suppressing functions but also enhance oncogenic characteristics.Recent data indicate that mutp53 is strongly associated with poor prognosis and advanced cancers,making it an ideal target for the development of novel cancer therapies.This review summarizes the post-translational modifications of p53,the mechanisms of mutp53 accumulation,and its gain-of-function,based on previous findings.Additionally,this review discusses its impact on metabolic homeostasis,ferroptosis,genomic instability,the tumor microenvironment,and cancer stem cells,and highlights recent advancements in mutp53 research.展开更多
文摘Tumor protein p53 (TP53) mediates DNA repair and cell proliferation in growing cells. The TP53 gene is a tumor suppressor that regulates the expression of target genes in response to multiple cellular stress factors. Key target genes are involved in crucial cellular events such as DNA repair, cell cycle regulation, apoptosis, metabolism, and senescence. TP53 genetic variants and the activity of the wild-type p53 protein (WT-p53) have been linked to a wide range of tumorigenesis. Various genetic and epigenetic alterations, including germline and somatic mutations, loss of heterozygosity, and DNA methylation, can alter TP53 activity, potentially resulting in cancer initiation and progression. This study was designed to screen three reported mutations in the DNA-binding domain of the p53 protein in breast cancer, to evaluate the relative susceptibility and risk associated with breast cancer in the local population. Genomic DNA was isolated from 30 breast tumor tissues along with controls. Tetra and Tri ARMS PCR were performed to detect mutations in the TP53 coding region. For SNPs c.637C>T and c.733C>T, all analyzed cases were homozygous for the wild-type allele ‘C,’ while for SNP c.745A>G, all cases were homozygous for the wild-type allele ‘A.’ These results indicate no relevance of these three SNPs to cancer progression in our study cohort. Additionally, the findings from whole exon sequencing will help to predict more precise outcomes and assess the importance of TP53 gene mutations in breast cancer patients.
文摘TP53 is a tumor suppressor gene that is mutated in most cancer types and has been extensively studied in cancer research.p53 plays a critical role in regulating the expression of target genes and is involved in key processes such as apoptosis,cell cycle regulation,and genomic stability,earning it the title“guardian of the genome.”Numerous studies have demonstrated p53’s influence on and regulation of autophagy,ferroptosis,the tumor microenvironment,and cell metabolism,all of which contribute to tumor suppression.Alterations in p53,specifically mutant p53(mutp53),not only impair its tumor-suppressing functions but also enhance oncogenic characteristics.Recent data indicate that mutp53 is strongly associated with poor prognosis and advanced cancers,making it an ideal target for the development of novel cancer therapies.This review summarizes the post-translational modifications of p53,the mechanisms of mutp53 accumulation,and its gain-of-function,based on previous findings.Additionally,this review discusses its impact on metabolic homeostasis,ferroptosis,genomic instability,the tumor microenvironment,and cancer stem cells,and highlights recent advancements in mutp53 research.
