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  • Endothelin responds to damage

    images43In the laboratory of Fernando Rodriguez Pascual, Researcher, Center for Biological Research of the CSIC, are very interested in studying mechanisms regulating gene expression vasoconstrictor peptide endothelin-1 (ET-1) at both transcriptional and posttranscriptional . In a previous work, the group had reported that certain elements rich in adenine and uridine (AU-rich elements or ARE) present in the 3′-untranslated region (3′-UTR) of this gene contribute to the destabilization of mRNA.
    In the paper published in Molecular and Cellular Biology are proposed to analyze the factors and signaling pathways involved in this process of destabilization. The results have identified the glycolytic enzyme 3-glyceraldehyde phosphate dehydrogenase (GAPDH) as the major protein able to interact with ARE elements in the 3′-UTR of the gene for ET-1. The binding of GAPDH to these elements promotes the rapid degradation of mRNA. The study shows that GAPDH acts as a key sensor of oxidative stress. After a redox stimulus, during which the ratio reduced glutathione / oxidized glutathione decreases GAPDH key cysteine reacts with glutathione to form a mixed disulfide in a process called S-tiolación.

    The experiments show that the modified protein is unable to interact with ET-1 mRNA, resulting in a decoupling of its degradation, favoring its accumulation. With the mechanism described, the cells can respond dynamically to free radical damage through changes in the expression of certain genes, such as ET-1. This response is via the enzyme GAPDH, a protein originally thought unique metabolic function in glycolysis and, latterly, have been attributed other functions in processes such as cell death or DNA repair.

    Published on November 13, 2012 · Filed under: Bioscience; Tagged as: , , , , ,
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