Retraction Note to: WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation

Congenital Zika Syndrome (CZS) occurs in up to 42% of individuals exposed to ZIKV prenatally. Deregulation in gene expression and protein levels of components of the p53 signaling pathway, such as p53 and MDM2, due to ZIKV infection has been reported. Here, we evaluate functional polymorphisms in genes of the p53 signaling pathway as risk factors to CZS. Forty children born with CZS and forty-eight children exposed to ZIKV, but born without congenital anomalies were included in this study. Gestational and sociodemographic information as well as the genotypic and allelic frequencies of functional polymorphisms in TP53, MDM2, MIR605 and LIF genes were compared between the two groups. We found children with CZS exposed predominantly in the first trimester and controls in the third trimester (p<0.001). Moreover, children with CZS were predominantly from families with a lower socioeconomic level (p=0.008). We did not find a statistically significant association between the investigated polymorphisms and development of CZS; however, by comparing individuals with CZS and lissencephaly or without lissencephaly, we found a significative difference in the allelic frequencies of the TP53 rs1042522, which is associated with a more potent p53-induced apoptosis (p=0.007). Our findings suggest that the TP53 rs1042522 polymorphism should be better investigate as a genetic risk factor for the development of lissencephaly in children with CZS.

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THE MDM2 309T>G POLYMORPHISM CONTROLS THE MDM2-P53 SIGNALING PATHWAY AND DICTATES FUNCTIONAL OUTCOME AFTER STROKE

10.26226/morressier.58e389afd462b80292384a99 ◽

2017 ◽

Author(s):

María Esther Ramos-Araque

Keyword(s):

Functional Outcome ◽

Signaling Pathway ◽

P53 Signaling ◽

P53 Signaling Pathway

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The Molecular Docking of Flavonoids Isolated from Daucus carota as a Dual Inhibitor of MDM2 and MDMX

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892815666200226112506 ◽

2020 ◽

Vol 15 (2) ◽

pp. 154-164 ◽

Cited By ~ 1

Author(s):

Ijaz Muhammad ◽

Noor Rahman ◽

Gul E. Nayab ◽

Sadaf Niaz ◽

Mohibullah Shah ◽

...

Keyword(s):

Molecular Docking ◽

Cancer Therapy ◽

Natural Product ◽

Signaling Pathway ◽

In Silico ◽

P53 Protein ◽

Dual Inhibitor ◽

P53 Signaling ◽

In Silico Studies ◽

P53 Signaling Pathway

Background: Cancer is characterized by overexpression of p53 associated proteins, which down-regulate P53 signaling pathway. In cancer therapy, p53 activity can be restored by inhibiting the interaction of MDMX (2N0W) and MDM2 (4JGR) proteins with P53 protein. Objective: In the current, study in silico approaches were adapted to use a natural product as a source of cancer therapy. Methods: In the current study in silico approaches were adapted to use a natural product as a source of cancer therapy. For in silico studies, Chemdraw and Molecular Operating Environment were used for structure drawing and molecular docking, respectively. Flavonoids isolated from D. carota were docked with cancerous proteins. Result: Based on the docking score analysis, we found that compound 7 was the potent inhibitor of both cancerous proteins and can be used as a potent molecule for inhibition of 2N0W and 4JGR interaction with p53. Conclusion: Thus the compound 7 can be used for the revival of p53 signaling pathway function however, intensive in vitro and in vivo experiments are required to prove the in silico analysis.

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