Journal ArticleDOI
The codon 72 polymorphic variants of p53 have markedly different apoptotic potential.
Reads0
Chats0
TLDR
It is found that in cell lines containing inducible versions of alleles encoding the Pro72 and Arg72 variants, and in cells with endogenous p53, the Arg72 variant induces apoptosis markedly better than does the Pro 72 variant.Abstract:
The gene TP53, encoding p53, has a common sequence polymorphism that results in either proline or arginine at amino-acid position 72. This polymorphism occurs in the proline-rich domain of p53, which is necessary for the protein to fully induce apoptosis. We found that in cell lines containing inducible versions of alleles encoding the Pro72 and Arg72 variants, and in cells with endogenous p53, the Arg72 variant induces apoptosis markedly better than does the Pro72 variant. Our data indicate that at least one source of this enhanced apoptotic potential is the greater ability of the Arg72 variant to localize to the mitochondria; this localization is accompanied by release of cytochrome c into the cytosol. These data indicate that the two polymorphic variants of p53 are functionally distinct, and these differences may influence cancer risk or treatment.read more
Citations
More filters
Journal ArticleDOI
Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism
Maria J. Fuentes-Raspall,Isabel Caragol,Carmen Alonso,Teresa Ramón y Cajal,David Fisas,Alejandro Seoane,Nerea Carvajal,Sandra Bonache,Orland Diez,Sara Gutiérrez-Enríquez +9 more
TL;DR: The data suggest that the 72Pro TP53 allele may influence the IA of patients with radiotherapy toxicity, and indicate that late side effects induced by radiotherapy of BC are associated to low levels of IA.
Journal ArticleDOI
Correlation of telomere length shortening with TP53 somatic mutations, polymorphisms and allelic loss in breast tumors and esophageal cancer
Xiao-Dan Hao,Yue Yang,Xin Song,Zhao Xueke,Li-Dong Wang,Jun-Dong He,Qing-Peng Kong,Nelson L.S. Tang,Ya-Ping Zhang +8 more
TL;DR: The results support that the TP53 gene has a strong interaction with TL erosion in tumorigenesis and suggest that somatic p53 mutations, rs12951053 genotype CC and rs1042522 genotype contribute to erosion of telomeres, and TP53 allelic loss may be one of the representations of chromosomal instability caused by telomere erosion.
Journal ArticleDOI
An updated meta-analysis of the p53 codon 72 polymorphism and gastric cancer risk
TL;DR: This study suggests that, among Asians, the p53 codon 72 Arg/Arg genotype is associated with a modestly decreased risk of gastric cancer, and that this difference in genotype distribution may be associated with cancer stage, location, differentiation and metastasis.
Journal ArticleDOI
Association of p53 Arg72Pro polymorphism with bladder cancer: a meta-analysis.
TL;DR: This meta-analysis suggests that p53 Arg72Pro polymorphism is associated with increased risk of bladder cancer in Asians and further studies with larger participants worldwide are needed to validate the association.
Journal ArticleDOI
Genetic Susceptibility in Head and Neck Squamous Cell Carcinoma in a Spanish Population
Javier Fernández-Mateos,Raquel Seijas-Tamayo,Juan Carlos Adansa Klain,Miguel Pastor Borgoñón,Elisabeth Pérez-Ruiz,Ricard Mesia,Elvira del Barco,Carmen Salvador Coloma,Antonio Rueda Domínguez,Javier Caballero Daroqui,Encarnación Fernández Ruiz,Alberto Ocaña,Alberto Ocaña,Rogelio González-Sarmiento,Juan J. Cruz-Hernández +14 more
TL;DR: Several SNPs associated with HNC in a Spanish population are described, some of which were not described before in this tumour type.
References
More filters
Journal ArticleDOI
WAF1, a potential mediator of p53 tumor suppression
Wafik S. El-Deiry,Takashi Tokino,Victor E. Velculescu,Daniel B. Levy,Ramon Parsons,Jeffrey M. Trent,D Lin,W. Edward Mercer,Kenneth W. Kinzler,Bert Vogelstein +9 more
TL;DR: A gene is identified, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line and that could be an important mediator of p53-dependent tumor growth suppression.
Journal ArticleDOI
Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Chu-Xia Deng,Chu-Xia Deng,Pumin Zhang,J. Wade Harper,Stephen J. Elledge,Stephen J. Elledge,Philip Leder,Philip Leder +7 more
TL;DR: The results establish the role of p21CIP1/WAF1 in the G1 checkpoint, but suggest that the anti-apoptotic and theAnti-oncogenic effects of p53 are more complex.
Journal ArticleDOI
Protein regulation by monoubiquitin
TL;DR: Multi-ubiquitin chains at least four subunits long are required for efficient recognition and degradation of ubiquitylated proteins by the proteasome, but other functions of ubiquitin have been discovered that do not involve the protease.
Journal ArticleDOI
Role of a p53 polymorphism in the development of human papillomavirus-associated cancer.
Alan Storey,Miranda Thomas,Ann Kalita,Catherine A. Harwood,Daniela Gardiol,Fiamma Mantovani,Judith Breuer,Irene M. Leigh,Greg Matlashewski,Lawrence Banks +9 more
TL;DR: Allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygously for arginin 72 are about seven times more susceptible to HPV- associated tumorigenesis than heterozygotes.
Journal ArticleDOI
Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling
TL;DR: This work proposes a model where p53 can contribute to apoptosis by direct signaling at the mitochondria, thereby amplifying the transcription-dependent apoptosis of p53.