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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Primary open angle glaucoma was not found to be associated with p53 codon 72 polymorphism in a Brazilian cohort.
TL;DR: The p53 codon 72 Arg/Pro polymorphism is not associated with glaucoma in Brazilian patients and the distribution of this polymorphism in 104 unrelated POAG patients and in 58 normal healthy individuals without history of POAG is examined.
Journal ArticleDOI
TP53 gene polymorphism: Importance to cancer, ethnicity and birth weight in a Brazilian cohort
Helena Strelow Thurow,Ricardo Lanzetta Haack,Fernando Pires Hartwig,Isabel O. Oliveira,Odir Antônio Dellagostin,Denise Petrucci Gigante,Bernardo L. Horta,Tiago Collares,Fabiana Kömmling Seixas +8 more
TL;DR: The Arg72Pro SNP was strongly associated with important epidemiological variables confirming that genetic profiles on cohort studies can improve the understanding of the susceptibility of diseases and its risk factors.
Journal ArticleDOI
p53 Codon 72 Polymorphism and Gastric Cancer Risk in a Chinese Han Population
TL;DR: This study suggests that the p53 codon 72 polymorphism may be associated with gastric cancer in Chinese Han patients, and that difference in genotype distribution may beassociated with the location and stage of Gastric cancer.
Journal ArticleDOI
Colorectal cancer: a researcher’s perspective of the molecular angel’s gone eccentric in the Vale of Kashmir
TL;DR: This review searched the various literature databases including Medline, PubMed, ASCO abstracts, and ESMO abstracts for the papers regarding colorectal cancer published in English using the terms “Kashmir,” “colorecto-colon cancer,’ “rectal cancer” and “carcinogenesis” to share what the authors know so far about the molecular carcinogenesis of CRC in Kashmir.
Journal Article
Human papillomavirus tumor-infiltrating T-regulatory lymphocytes and P53 codon 72 polymorphisms correlate with clinical staging and prognosis of oropharyngeal cancer
Massimo Rittà,Vincenzo Landolfo,Jasenka Mazibrada,Marco De Andrea,Valentina Dell'Oste,Valeria Caneparo,Alberto Peretti,Carlo Giordano,Giancarlo Pecorari,Massimiliano Garzaro,Santo Landolfo +10 more
TL;DR: The presence of HPV may trigger a stronger immune response and may be considered a reliable marker for clinical staging and a more favorable prognosis of oropharyngeal carcinoma.
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.