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The antitumor effect of GCN2 kinase: the relationship between nutritional stress, protein synthesis and skin cancer

17th national competition for scientific and technical research

Metabolism and cancer

Senior Researcher : César Jesús de Haro Castella

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Research Centre or Institution : Centro de Biología Molecular "Severo Ochoa". CSIC-Universidad Autónoma de Madrid


The response to stress allows live beings to respond and adapt to a changing environment which exposes them to radiation, temperature changes, toxic agents and a lack of food. The mammalian stress response not only regulates their capacity for adaptation to their environment but also in some way determines the speed at which organisms age and develop pathologies associated with age. In this project we propose to explore the connection between pathology and the response to two specific types of stress: ultraviolet radiation (UV) and nutritional restriction. GCN2, one of the kinases of the eIF2 translation factor, responds to both types of stress, promoting a reprogramming of protein synthesis that triggers an integrated response to the stress. Nevertheless, the scope of this adaptive response and its involvement in the natural process of ageing and some pathologies associated with the latter, such as cancer, have not been explored to date. The availability of mice and cell lines lacking GCN2 kinase now allows us to systematically seek an answer to this question. To this end we therefore propose to use this project to evaluate whether the presence of GCN2 in cells and its permanent or transitory activation, due to the privation of amino acids in an animal diet, affects the appearance of cutaneous lesions of a tumoral type in mice exposed to UV radiation. We will also study the role of this kinase in cell survival in cases of nutritional stress and UV radiation.

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