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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Acetylation of the Cell-Fate Factor Dachshund Determines p53 Binding and Signaling Modules in Breast Cancer
Ke Chen,Kongming Wu,Michael Gormley,Adam Ertel,Jing Wang,Wei Zhang,Jie Zhou,Gabriele Disante,Zhiping Li,Hallgeir Rui,Andrew A. Quong,Steven B. McMahon,Haiteng Deng,Michael P. Lisanti,Chenguang Wang,Richard G. Pestell +15 more
TL;DR: DACH1 inhibits breast cancer cellular growth in an NAD and p53-dependent manner through direct protein-protein association through directprotein- protein association.
Journal ArticleDOI
The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area
Chao-Yuan Huang,Chien Tien Su,Jan Show Chu,Shu Pin Huang,Yeong-Shiau Pu,Hsiu Yuan Yang,Chi Jung Chung,Chia Chang Wu,Yu Mei Hsueh +8 more
TL;DR: This is the first study to show that a variant genotype of p53 Arg(72)Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area.
Journal ArticleDOI
Association between polymorphisms in RAPGEF1, TP53, NRF1 and type 2 diabetes in Chinese Han population
Lili Qu,Bangshun He,Yuqin Pan,Yongfei Xu,Chan Zhu,Zhipeng Tang,Qian Bao,Fuliang Tian,Shukui Wang +8 more
TL;DR: It is demonstrated that the polymorphism in TP53 (rs1042522) was associated with type 2 diabetes, and that potential interaction of TP53, RAPGEF1, or NRF1 increased the risk of type 2 Diabetes in the Chinese Han population.
Journal ArticleDOI
Proline homozygosity in codon 72 of TP53 is a factor of susceptibility to nasopharyngeal carcinoma in Tunisia
Boutheina Hadhri-Guiga,Nabil Toumi,Abdelmajid Khabir,Tahia Sellami-Boudawara,A. Ghorbel,Jamel Daoud,Mounir Frikha,Ali Gargouri,Raja Mokdad-Gargouri +8 more
TL;DR: Evidence is provided that individuals with the Pro/Pro genotype have an increased risk of developing NPC in Tunisia and no significant difference was observed between TP53 codon 72 polymorphism and age, sex, histological grade, and metastasis.
Journal ArticleDOI
Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis.
Thomas LaFramboise,Ninad Dewal,Katherine Wilkins,Itsik Pe'er,Matthew L. Freedman,Matthew L. Freedman +5 more
TL;DR: The results support the notion that combining germline and tumor genetic data can identify regions relevant to cancer biology, and demonstrate synergy between preferential allelic amplification and expression in DOCK4 and EGFR.
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.