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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Journal ArticleDOI
TP53 codon 72 polymorphism in pigmentary phenotypes
TL;DR: The findings indicate susceptibility to sun exposure when this phenotype (eye colour) occurs simultaneously with Pro/Pro genotype, and a significant association between the genotype Pro/ pro and blue/green eyes among participants who presented redness.
Journal ArticleDOI
Analysis of TP53 polymorphisms in North Indian sporadic esophageal cancer patients.
Sukhpreet Kaur,Vasudha Sambyal,Kamlesh Guleria,Mridu Manjari,Meena Sudan,Manjit Singh Uppal,Neeti Rajan Singh,Gursimran Singh,Harpreet Singh +8 more
TL;DR: Among the five TP53 polymorphisms investigated, only p.R72P polymorphism may contributes to EC susceptibility and the RP-A1A1-GG genotype combination shows significant risk for EC.
Journal ArticleDOI
Evaluation of CTNNB1 and TP53 variability in patients with hepatocellular carcinoma and occult hepatitis B virus infection.
Carlo Saitta,Marika Lanza,Antonio Bertuccio,Lazzara S,Giuseppe Navarra,Giovanni Raimondo,Teresa Pollicino +6 more
TL;DR: Investigation of the genetic heterogeneity of CTNNB1 exon 3 and all of the TP53 exons in tumor DNA extracts from a unique cohort of 61 HCC patients found CTNNb1 and TP53 somatic mutations seem to be a rare event in patients with HCC in this area and in cases with either overt or occult HBV infection.
Journal ArticleDOI
Association between p53 codon 72 polymorphisms and clinical outcome of nasopharyngeal carcinoma.
TL;DR: It is shown that variants in p53 codon 72 may be an independent predictor for PFS and OS of NPC patients and was associated with a longer median PFS time than those with Arg/Arg variants.
Journal ArticleDOI
No association of p53 codon 72 polymorphism with idiopathic recurrent pregnancy loss in Korean population
Sang Ho Yoon,Young Min Choi,Jin Ju Kim,Jin Ju Kim,Min A. Hong,Sung Ki Lee,Kwang Moon Yang,Eun Chan Paik +7 more
TL;DR: The codon 72 polymorphism in the p53 gene did not show any correlation with idiopathic RPL in Korean women, implying that it may not be susceptible allelic variants or be insufficient to cause RPL.
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.