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Study of the regulation of protein PSTPIP1 via tyrosine phosphorylation and its contribution to the aetiology of the PAPA autoinflammatory disease

15th National Research Competition in Life and Earth Sciences

Rare diseases

Senior Researcher : Andrés Alonso García

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Research Centre or Institution : Instituto de Biología y Genética Molecular. CSIC. Valladolid.

Abstract

PSTPIP1 is involved in activation of the inflammasome, which generates the active form of IL 1beta. The mutations A230T and E250Q in PSTPIP1 cause the autoinflammatory disease known as PAPA. These mutations affect a region of this protein that interacts with the PTPPEST tyrosine phosphatase, blocking its interaction, which leads to increased phosphorylation of PSTPIP1. At present it is unknown what role tyrosine phosphorylation plays in regulating PSTPIP1 and what importance it can have for the function of this protein in inflammatory response. It is also unknown which stimuli and signalling pathways are involved in the phosphorylation of PSTPIP1. This project proposes to study the physiological function of PSTPIP1 in the inflammatory response and determine the molecular mechanisms by which PSTPIP1 intervenes in the pathogenesis of PAPA autoinflammatory disease.

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