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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Regulation of p53 by Mdm2: Fate Is in the Numbers
Ayelet Shmueli,Moshe Oren +1 more
TL;DR: The p53 tumor suppressor protein is normally restrained by the Mdm2 oncoprotein, which promotes p53 ubiquitination, but in a recent issue of Science, report that p53 may face two alternative fates, depending on MDM2 levels.
Journal ArticleDOI
p53 codon 72 alleles influence the response to anticancer drugs in cells from aged people by regulating the cell cycle inhibitor p21WAF1.
Stefano Salvioli,Massimiliano Bonafè,Cristiana Barbi,Gianluca Storci,Chiara Trapassi,Francesca F. Tocco,Silvia Gravina,Matteo Rossi,Luca Tiberi,Chiara Mondello,Daniela Monti,Claudio Franceschi +11 more
TL;DR: It is concluded that the functional difference between the two p53 codon 72 alleles exerts a broadimpact on the capability of cell from aged people to respond to stressors such as cytotoxic drugs.
Journal ArticleDOI
TP53 Pro47Ser and Arg72Pro polymorphisms and colorectal cancer predisposition in an ethnic Kashmiri population.
Aga Syed Sameer,Zaffar Amin Shah,Nidda Syeed,Mujeeb Zafar Banday,S M Bashir,B A Bhat,Mushtaq A. Siddiqi +6 more
TL;DR: Arg72Pro SNP is associated with susceptibility to developing CRC in this ethnic Kashmiri population, and significant association of the Pro/Pro mutant with tumor location, nodal status/higher tumor grade and bleeding per rectum/constipation is found.
Journal ArticleDOI
p53 in the cytoplasm: a question of overkill?
Nicole Baptiste,Carol Prives +1 more
TL;DR: The tumor suppressor p53 regulates cellular responses to stress by serving in the nucleus to regulate transcription of genes involved in processes including cell cycle arrest, DNA repair, and apoptosis.
Journal ArticleDOI
MDM2 SNP 309 and p53 codon 72 polymorphisms are associated with the outcome of oral carcinoma patients receiving postoperative irradiation.
Hsi Feng Tu,Hong Wen Chen,Shou Yen Kao,Shu Chun Lin,Chung Ji Liu,Chung Ji Liu,Chung Ji Liu,Kuo Wei Chang,Kuo Wei Chang +8 more
TL;DR: It is identified that both MDM2 SNP309 and p53 codon 72 SNP could be useful factors for evaluating the outcome of advanced OSCC treated with adjuvant radiation.
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.