iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72–polymorphic p53

Bergamaschi, Daniele; Samuels, Yardena; Sullivan, Alice; Zvelebil, Marketa; Breyssens, Hilde; Bisso, Andrea; Sal, Giannino Del; Syed, Nelofer; Smith, Paul J.; Gasco, Milena; Crook, Tim; Lü, Xin

doi:10.1038/ng1879

Cited by 230 publications

(227 citation statements)

References 28 publications

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“…This finding is in accordance with Mantovani et al (2007) and Bergamaschi et al (2006) We also found the p53 (Arg) (Pro /Arg) variant are higher in the normal subjects. Variation in apoptotic index also correlated with the change in the pattern of Arg/Arg allele in various diseases showing that this allele may prevent the carcinogenic changes by stimulating the Apoptosis in the damaged epithelial cells.…”

Section: Discussionsupporting

confidence: 90%

Helicobacter pylori Infection and a P53 Codon 72 Single Nucleotide Polymorphism: a Reason for an Unexplained Asian Enigma

Pandey¹,

Misra²,

Misra³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Aim: P53, the most commonly mutated tumor suppressor gene in all types of human cancer, is involved in cell cycle arrest and control of apoptosis. Although p53 contains several polymorphic sites, the codon 72 polymorphism is by far more common. There are divergent reports but many studies suggest p53 pro/pro SNP may be associated with susceptibility to developing various cancers in different regions of the world. The present study aimed to find any correlation between H. pylori infection and progression of carcinogenesis, by studying apoptosis and the p53 gene in gastric biopsies from north Indian population. Materials and Methods: A total of 921 biopsies were collected and tested for prevalence of H. pylori by rapid urease test (RUT), imprint cytology and histology. Apoptosis was studied by the TUNEL method. Analysis of p53 gene polymorphism at codon 72 was accomplished by PCR using restriction enzyme BstU1. Observation: Out of 921 samples tested 56.7% (543) were H. pylori positive by the three techniques. The mean apoptotic index (AI) in the normal group was 2.12, while gastritis had the maximum 4.24 followed by gastric ulcer 2.28, gastropathy 2.22 and duodenal ulcer 2.08. Mean AI in cases with gastric cancer (1.72) was less than the normal group. The analysis of p53 72 SNP revealed that p53 (Arg/Arg), (Pro /Arg) variant are higher (40.59% & 33.66%) as compared to p53 pro/pro variant (25.74%) inthe healthy population. Conclusions: The North Indian population harbors Arg or Pro/Arg SNP that is capable of withstanding stress conditions; this may be the reason of low incidence of gastric disease in spite of high infection with H. pylori. There was no significant association with H. pylori infection and AI. However, there is increased apoptosis in gastritis which may occur independent of H. pylori or p53 polymorphism.

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Section: Discussionsupporting

confidence: 90%

Helicobacter pylori Infection and a P53 Codon 72 Single Nucleotide Polymorphism: a Reason for an Unexplained Asian Enigma

Pandey¹,

Misra²,

Misra³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Interestingly and importantly, ASPP family members also bind to the prolin rich region of p53 in addition to the DNA binding domain, which displays polymorphic loci at codon 72 in humans ( Figure 6). Bergamaschi et al (2006) described selective regulation of codon 72 variants by ASPP family members, particularly iASPP, bind to and control the activity of p53Pro72 more efficiently than that of p53Arg72, indicating that p53Arg72 activates apoptosis more capably than p53Pro72 due to getaway from negative regulation by iASPP. Hence, the most efficient way to inactivate the apoptotic function of p53Arg72 in human tumorigenesis is by intragenic mutation.…”

Section: Aspps: Interaction With P53mentioning

confidence: 99%

Recent Candidate Molecular Markers: Vitamin D Signaling and Apoptosis Specific Regulator of p53 (ASPP) in Breast Cancer

Patel

Patel²,

Patel³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…The frequency of the allele encoding p53Pro72 is closely linked to latitude and is much higher in populations living near the equator suggesting that p53Pro72 is selected in an environment with high levels of UV light (Sjalander et al, 1995). A novel mechanism by which the ASPP family members selectively regulate the apoptotic function of p53Pro72 and p53Arg72 has been described (Bergamaschi et al, 2006). iASPP has a higher binding affinity to p53Pro72 than to p53Arg72, and preferentially modulates the apoptotic potential of p53Pro72 over p53Arg72.…”

Section: Iaspp Modulates the Apoptotic Function Of P53 Codon 72 Polymmentioning

confidence: 99%

ASPP: a new family of oncogenes and tumour suppressor genes

2007

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The apoptosis stimulating proteins of p53 (ASPP) family consists of three members, ASPP1, ASPP2 and iASPP. They bind to proteins that are key players in controlling apoptosis (p53, Bcl-2 and RelA/p65) and cell growth (APCL, PP1). So far, the best-known function of the ASPP family members is their ability to regulate the apoptotic function of p53 and its family members, p63 and p73. Biochemical and genetic evidence has shown that ASPP1 and ASPP2 activate, whereas iASPP inhibits, the apoptotic but not the cellcycle arrest function of p53. The p53 tumour suppressor gene, one of the most frequently mutated genes in human cancer, is capable of suppressing tumour growth through its ability to induce apoptosis or cell-cycle arrest. Thus, the ASPP family of proteins helps to determine how cells choose to die and may therefore be a novel target for cancer therapy.

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iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72–polymorphic p53

Cited by 230 publications

References 28 publications

Helicobacter pylori Infection and a P53 Codon 72 Single Nucleotide Polymorphism: a Reason for an Unexplained Asian Enigma

Helicobacter pylori Infection and a P53 Codon 72 Single Nucleotide Polymorphism: a Reason for an Unexplained Asian Enigma

Recent Candidate Molecular Markers: Vitamin D Signaling and Apoptosis Specific Regulator of p53 (ASPP) in Breast Cancer

ASPP: a new family of oncogenes and tumour suppressor genes

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