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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The association between the TP53 Arg72Pro polymorphism and colorectal cancer: An updated meta-analysis based on 32 studies.
TL;DR: It is found that the TP53 Arg72Pro polymorphism CC genotype was not significantly associated with CRC risk in the overall population, but subgroup analysis based on ethnicity revealed an increased risk of CRC among Asians.
Journal ArticleDOI
Polymorphisms in apoptosis-related genes in cutaneous melanoma prognosis: sex disparity
Cristiane Oliveira,Gustavo Jacob Lourenço,José Augusto Rinck-Junior,Aparecida Machado de Moraes,Carmen Silvia Passos Lima +4 more
TL;DR: Preliminary evidence is presented that inherited abnormalities on TP53, MDM2 and BCL2 genes, enrolled in apoptosis pathways, have a pivotal role in differences of outcomes in women and men with CM.
Journal ArticleDOI
Germline TP53 mutational spectrum in French Canadians with breast cancer
Suzanna L. Arcand,Mohammed Reza Akbari,Anne-Marie Mes-Masson,Diane Provencher,William D. Foulkes,William D. Foulkes,William D. Foulkes,Steven A. Narod,Patricia N. Tonin,Patricia N. Tonin +9 more
TL;DR: Six new TP53 mutations were identified in French Canadians, where two each occurred in independently ascertained cases/families and none were consistent with features of Li-Fraumeni syndrome families.
Journal ArticleDOI
Endometrial receptivity and pregnancy outcome
TL;DR: This overview reports the most relevant knowledge and recent advances in the study of implantation processes from the perspective of the endometrium, often considered as being the main barrier for a successful pregnancy initiation.
Journal ArticleDOI
Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas
Zahra Montazeri,Evropi Theodoratou,Christine Nyiraneza,Maria Timofeeva,Wanjing Chen,Victoria Svinti,Shanya Sivakumaran,Gillian Gresham,Laura Cubitt,Luis G. Carvajal-Carmona,Monica M. Bertagnolli,Ann G. Zauber,Ian Tomlinson,Susan M. Farrington,Malcolm G. Dunlop,Harry Campbell,Harry Campbell,Julian Little +17 more
TL;DR: The first comprehensive field synopsis that catalogues all genetic association studies on CRA, with a parallel online database, is reported, reflecting the lower volume of evidence and associated lack of statistical power to detect associations of the magnitude typically observed for genetic variants and chronic diseases.
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.