Journal ArticleDOI
The codon 72 polymorphic variants of p53 have markedly different apoptotic potential.
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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
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Association of TP53 codon 72 polymorphism with cervical cancer risk in Chinese women.
TL;DR: The findings suggest that the TP53 codon 72 polymorphism may be implicated in cervical carcinogenesis, with the Arg/Arg genotype being associated with an increased susceptibility for this malignancy in the southern Chinese population.
Journal ArticleDOI
Gene-gene interactions in gastrointestinal cancer susceptibility.
TL;DR: It is proposed that three modes of biological interaction underlie the molecular mechanisms for statistical epistasis in susceptibility to gastrointestinal cancers, and this is likely true for other complex diseases as well.
Journal ArticleDOI
An evaluation of the polymorphisms Ins16bp and Arg72Pro in p53 as breast cancer risk modifiers in BRCA1 and BRCA2 mutation carriers
Ana Osorio,Marina Pollán,G Pita,Rita K. Schmutzler,Beatrix Versmold,Christoph Engel,Alfons Meindl,Norbert Arnold,Sabine Preisler-Adams,Dieter Niederacher,W. Hofmann,Dorothea Gadzicki,Anna Jakubowska,Ute Hamann,Jan Lubinski,Aleksandra Tołoczko-Grabarek,Cezary Cybulski,Tadeusz Dębniak,Gemma Llort,Drakoulis Yannoukakos,Orland Diez,Bernard Peissel,Paolo Peterlongo,Paolo Radice,Tuomas Heikkinen,Heli Nevanlinna,P L Mai,J T Loud,Lesley McGuffog,Antonis C. Antoniou,Javier Benítez +30 more
TL;DR: This study evaluated the association between a p53 haplotype combining the absence of the 16-bp insertion and the presence of proline at codon 72 and an earlier age at the onset of the first primary tumour in BRCA2 mutation carriers in the Spanish population.
Journal ArticleDOI
Polymorphism of the p53 tumor suppressor gene is associated with susceptibility to uterine leiomyoma
Dominik Denschlag,Herta Bettendorf,Dirk Watermann,Christoph Keck,Clemens Tempfer,Detlef Pietrowski +5 more
TL;DR: Carriage of the p53 polymorphism at codon 72 predicts the susceptibility to leiomyoma in a Caucasian population and may contribute to the pathogenesis of uterine leiomeoma.
Journal ArticleDOI
Lung cancer risk in relation to TP53 codon 47 and codon 72 polymorphism in Bangladeshi population
Md. Shaki Mostaid,Maizbha Uddin Ahmed,Mohammad Safiqul Islam,Muhammad Shahdaat Bin Sayeed,Abul Hasnat +4 more
TL;DR: It is concluded that not Pro47Ser SNP but Arg72Pro SNP is involved in susceptibility to developing lung cancer, at least in Bangladeshi population.
References
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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.