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The molecular bases of disease: biointeractomics of programmed cell death

17th national competition for scientific and technical research

Interactome: pathological implications

Senior Researcher : Miguel Ángel De la Rosa Acosta

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Research Centre or Institution : cicCartuja, Instituto de Bioquímica Vegetal y Fotosíntesis. Universidad de Sevilla-CSIC


The control of cell survival and death is essential for cellular homeostasis, and dysfunction of the latter causes many diseases. This project aims to characterise the network of interactions between proteins (or biointeractome) by focusing on cytochromec, which regulates programmed cell death (or apoptosis). The activation of Apaf-1 (apoptotic protease activating factor 1) in cytoplasm was until very recently the only known function of cytochrome c released by the mitochondria, but recent findings by our group indicate that the haemoprotein is the key node in a biointeractomic network conserved in the evolution of plants and humans (Martínez Fábregas et al., 2013; 2014). The aforementioned pro-apoptotic biointeractome spreads in the cytoplasm and nucleus until it interferes with regulation of the p53 tumour suppressor. We therefore aim to analyse the interactions of cytochrome c with the aforementioned target proteins that regulate p53 in structural and functional terms, using the techniques available in the recently created Plataforma de Interacciones Biomoleculares del cicCartuja.

Given that cytochrome c suffers post-translational modifications which alter its structure and function, we also intend to determine how the phosphorylation of certain thyrosines modifies the affinity of cytochrome c for its new targets. In this way, the goal is to construct the biointeractomic network of phosphorylated cytochrome c, the result of which will be validated by transverse biophysical techniques, an innovative approach used with success by our team in previous studies (www.ibvf.csic.es/en/biointeractomics).

The execution of the proposed tasks will make it possible to determine common epitopes at the sites where cytochrome c binds to its new apoptotic targets and, likewise, learn more about the molecular bases of diseases, above all neurodegenerative ones and cancer, thereby opening up a new route for the design of new drugs.

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