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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Tissue-specific apoptotic effects of the p53 codon 72 polymorphism in a mouse model.
TL;DR: Evidence is presented that this polymorphism regulates the ability to cooperate with NF-kB and induce apoptosis in p53 in a tissue-specific manner, which supports the premise that modeling human polymorphisms in the mouse represents a powerful tool to assess the impact of these variants on cancer risk, progression and therapy.
Journal Article
Association of polymorphisms in APOE, p53, and p21 with primary open-angle glaucoma in Turkish patients
TL;DR: The study found no link between polymorphisms in APOE, p53, and p21 genes and POAG in Turkish patients, although a larger sample is required to elucidate the role of these polymorphismsIn the pathogenesis and course of glaucoma.
Journal ArticleDOI
p53 codon 72 Pro homozygosity increases the risk of cutaneous melanoma in individuals with dark skin complexion and among noncarriers of melanocortin 1 receptor red hair variants.
I. Stefanaki,Alexandros Stratigos,Gerasimos Dimisianos,V. Nikolaou,O. Papadopoulos,Dorothea Polydorou,Helen Gogas,D. Tsoutsos,P. Panagiotou,E. Kanavakis,Ch. Antoniou,Andreas Katsambas +11 more
TL;DR: P53Arg and p53Pro exhibit differences in various biological activities, such as cell‐cycle arrest and induction of apoptosis, with contradictory results in several human malignancies, including cutaneous cancers.
Journal ArticleDOI
p53 codon 72 polymorphism and Hematological Cancer Risk: An Update Meta-Analysis
TL;DR: This meta-analysis indicates that the p53 Arg72Pro polymorphism may contribute to susceptibility to non-Hodgkin lymphomas.
Journal ArticleDOI
Evaluation of TP53 mutations with the AmpliChip p53 research test in chronic lymphocytic leukemia: correlation with clinical outcome and gene expression profiling.
Sabina Chiaretti,Simona Tavolaro,Marilisa Marinelli,Monica Messina,Ilaria Del Giudice,Francesca Romana Mauro,Simona Santangelo,Alfonso Piciocchi,Nadia Peragine,Sim Truong,Nancy Patten,Emanuela M. Ghia,Isabella Torrente,Maria Stefania De Propris,Mauro Nanni,Jeffrey Lawrence,Anna Guarini,Robin Foà +17 more
TL;DR: A high percentage of TP53 mutations are found in CLL with unfavorable outcome and a significant association between TP53 aberrations and del(17p) was recorded, and specific gene expression profiles are recognized for TP53 alterations.
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.