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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Prognostic value of the TP53 Arg72Pro single-nucleotide polymorphism and susceptibility to medulloblastoma in a cohort of Brazilian patients
Raimundo Miranda de Carvalho,Raimundo Miranda de Carvalho,Giovanny R. Pinto,P.D.L. Lima,Carolina Rosal Teixeira de Souza,Adriana Costa Guimarães,Leticia Martins Lamarão,Juan A. Rey,Rommel Rodríguez Burbano +8 more
TL;DR: It is suggested that, although there is no association between the TP53 Arg72Pro SNP and medulloblastoma risk, the Pro/Pro genotype is associated with shorter overall survival of patients submitted to adjuvant therapy.
Journal ArticleDOI
TP53 and XRCC1 polymorphisms and breast cancer prognosis: a case-case study
Marina Silva Rodrigues,Camila Almeida Machado,Dante Pagnoncelli,Elizabeth Avvad,Júlio César da Paixão,Claudia Vitoria de Moura Gallo +5 more
TL;DR: XRCC1 is important in the base excision repair process(BER) and has two common polymorphisms in codons194 (Arg194Trp) and 399 (Arg399Gln) that affect the aminoacid sequence.
Journal ArticleDOI
Aneuploidy of chromosome 8 and mutation of circulating tumor cells predict pathologic complete response in the treatment of locally advanced rectal cancer.
Juefeng Wan,Xue Qin Li,Jing Zhang,Li Feng Yang,Jianlong Zhu,Gui Chao Li,Liping Liang,Lijun Shen,Hui Zhang,Jing Li,Yi Tong Zhang,Chang Yue Chen,Zhen Zhang +12 more
TL;DR: Results suggest that ≥5 copies of chromosome 8 and 8 nonsynonymous mutations in ARID1A, HDAC1, APC, ERBB3, TP53, AMER1 AR in CTCs were associated with pathCR, which should be validated further in larger prospective studies.
Journal ArticleDOI
Arg72Pro polymorphism of TP53 gene and the risk of skin cancer: a meta-analysis.
TL;DR: It is indicated that TP53 Arg72Pro polymorphism probably had little association with skin cancer susceptibility mainly in Caucasians, however, larger sample-size studies are required to verify the conclusion as low statistical powers.
Journal ArticleDOI
Maternal SNPs in the p53 pathway: risk factors for trisomy 21?
Juliano André Boquett,Ana Paula Carneiro Brandalize,Lucas Rosa Fraga,Lavinia Schuler-Faccini +3 more
TL;DR: The effect of the combined genotypes among TP53, MDM2 and USP7 genes indicates a possible role of TP53 and its regulatory pathway as a risk factor for aneuploidy.
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.