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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Prognostic role of p53 codon 72 polymorphism in gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy.
TL;DR: It is suggested that p53 codon 72 polymorphism appears to be an independent prognostic factor in gastric cancer patients treated with 5-FU-based adjuvant chemotherapy.
Journal ArticleDOI
Role of p53 codon 72 arginine allele in cell survival in vitro and in the clinical outcome of patients with advanced breast cancer.
Ivan Vannini,Wainer Zoli,Anna Tesei,Marco Rosetti,Pasquale Sansone,Gianluca Storci,Alessandro Passardi,Ilaria Massa,Marianna Ricci,D. Gusolfino,Francesco Fabbri,Paola Ulivi,Giovanni Brigliadori,Dino Amadori,Massimiliano Bonafè +14 more
TL;DR: A molecular explanation for the association of the arginine allele with tumor aggressiveness and treatment resistance in advanced breast cancer is provided.
Journal ArticleDOI
In B-CLL, the codon 72 polymorphic variants of p53 are not related to drug resistance and disease prognosis
Isrid Sturm,Andrew G. Bosanquet,Michael Hummel,Bernd Dörken,Bernd Dörken,Peter T. Daniel,Peter T. Daniel +6 more
TL;DR: Functional relevance of the codon 72 single nucleotide (SNP) polymorphism for cell death sensitivity following exposure to clinically employed cytotoxic drugs and γ-irradiation is addressed.
Journal ArticleDOI
Effect of the p53 codon 72 and intron 3 polymorphisms on non-small cell lung cancer (NSCLC) prognosis.
Laura Boldrini,Silvia Gisfredi,Silvia Ursino,Marco Lucchi,Giordana Greco,Alfredo Mussi,Valentina Donati,Gabriella Fontanini +7 more
TL;DR: Support is provided for the prognostic effects of the multi-variant alleles from p53 exon 4 and intron 3, resulting in a significantly poorer prognosis in NSCLC, highlighting the value of examining multiple polymorphisms in genes to improve survival estimates.
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.