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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Risk genes in head and neck cancer: A systematic review and meta-analysis of last 5 years
TL;DR: The aim of this work was to identify risk genes related to the development and progression of squamous cell carcinoma head and neck (SCCHN) and do a meta-analysis of available estimates, showing no significant association between different allelic variants of Arg72Pro rs1042522 and SCCHN risk.
Journal ArticleDOI
Gene polymorphisms, apoptotic capacity and cancer risk
TL;DR: Meta-analysis of TP53 genotyping studies has provided evidence for the association between apoptosis-deficient TP 53 genotype and tumor susceptibility, and systematic analysis of cancer-predisposing relevance of other apoptotic gene SNPs remains to be done.
Journal ArticleDOI
Polymorphisms in p53, GSTP1 and XRCC1 predict relapse and survival of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy
Zhaohui Huang,Dong Hua,Xiang Du +2 more
TL;DR: Testing for p53 Arg72Pro, GSTP1 Ile105Val, and XRCC1 Arg399Gln polymorphisms may allow identification of gastric cancer patients who will benefit from oxaliplatin-based adjuvant chemotherapy.
Journal ArticleDOI
p53 codon 72 polymorphism associated with risk of human papillomavirus-associated squamous cell carcinoma of the oropharynx in never-smokers.
Xuemei Ji,Ana C Candia Solari Neumann,Ana C Candia Solari Neumann,Erich M. Sturgis,Karen Adler-Storthz,Kristina R. Dahlstrom,John T. Schiller,Qingyi Wei,Guojun Li +8 more
TL;DR: It is suggested that p53 codon 72 variant genotypes modify the risk of HPV16-associated SCCOP and may be markers of genetic susceptibility to HPV16's squamous cell carcinoma of the oropharynx, especially among never-smokers.
Journal ArticleDOI
TP63 and TP73 in cancer, an unresolved “family” puzzle of complexity, redundancy and hierarchy
Antonio Costanzo,Natalia Pediconi,Alessandra Narcisi,Francesca Guerrieri,Laura Belloni,Francesca Fausti,Elisabetta Botti,Massimo Levrero +7 more
TL;DR: The p53 family as a whole behaves as a signaling “network” that integrates developmental, metabolic and stress signals to control cell metabolism, differentiation, longevity, proliferation and death.
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.