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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Association of p53 polymorphisms and colorectal cancer : Modulation of risk and progression
Enzo Mammano,Claudio Belluco,Massimiliano Bonafè,Fabiola Olivieri,Elena Mugianesi,Cristiana Barbi,Michele Mishto,Marco Cosci,Claudio Franceschi,Mario Lise,Donato Nitti +10 more
TL;DR: The findings indicate that the p53 codon 72 polymorphisms are associated with a higher risk of CRC and are related with more advanced and undifferentiated tumours.
Journal ArticleDOI
Adenovirus-mediated p53 tumor suppressor gene therapy of osteosarcoma
TL;DR: In this paper, a contemporary summarization of the current status of adenovirus-mediated p53 gene therapy of osteosarcoma is presented, and the advancement in our understanding of p53 tumor suppressor activity, the molecular biology of chemoresistant OS, and recent advances in tumor targeting with adnoviral vectors are also addressed.
Journal ArticleDOI
TP53 codon 72 polymorphism and colorectal cancer susceptibility: a meta-analysis
Jing-Jun Wang,Yuan Zheng,Liang Sun,Li Wang,Pengbo Yu,Jian-Hua Dong,Lei Zhang,Jing Xu,Wei Shi,Yu-Chun Ren +9 more
TL;DR: A meta-analysis suggested that the biologically usefulness of TP53 codon 72 polymorphism as a selection marker in colorectal cancer susceptibility may be very limited.
Journal ArticleDOI
Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations
Katsuhiro Masago,Shiro Fujita,Miho Muraki,Akito Hata,Chiyuki Okuda,Kyoko Otsuka,Reiko Kaji,Jumpei Takeshita,Ryoji Kato,Nobuyuki Katakami,Yukio Hirata +10 more
TL;DR: It is shown that next-generation sequencing (NGS) is able to detect EGFR T790M mutations in cases not readily diagnosed by other conventional methods, suggesting the need for alternative treatment strategies, with PCR-based NGS playing an important role in disease diagnosis.
Journal ArticleDOI
Linking environmental carcinogen exposure to TP53 mutations in human tumours using the human TP53 knock-in (Hupki) mouse model: Cancer aetiology and TP53 mutations
TL;DR: The Hupki embryo fibroblast immortalization assay has sufficient specificity to make it applicable to other environmental mutagens that putatively play a role in cancer aetiology, but has several limitations that could be addressed by future developments, in order to improve its sensitivity and selectivity.
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.