Influence of protein prenylation and its modulatio.. (Pren-IBD)
Influence of protein prenylation and its modulation on the immune system
Start date: Aug 1, 2012,
End date: Jul 31, 2014
Prenylation is a postranslational process leading to changes in protein structure due to the incorporation of a lipidic moiety that significantly modifies their physicochemical properties and their behaviour. Prenylation is therefore a crucial step for key cell processes, such as interaction between proteins, cell and differentiation, cytoskeletal function and vesicular trafficking. The modification of prenylation is proposed as an attractive option in biological and therapeutic research, as its alteration can cause significant changes in cell biology. In fact, several prenylation inhibitors are currently included in preclinical and clinical research as anticancer agents (Sasaki M, 2003; Mach F, 2002). Many prenylation-modified processes can be considered of immune or inflammatory nature. In addition, a major substrate for prenylation reactions are small G proteins, which are involved in the activation of some relevant signaling pathways in the immune system. Thus, the immune response could be controlled by modulating prenylation.Specific cell-type inhibition of prenylation could be interesting allowing a better knowledge of its implication in cell biology considering several cell types related to the immune response. A novel technique for in vivo experiment is the genetic design of animals suffering from a cell-specific deficiency in the expression of a particular protein. This project is intended to study the influence of the lack of expression of one of the major enzymes involved in prenylation, GGTaseI, specifically in several cell types related to immune response, such as intestinal epithelial cells or lymphocytes. We will create strains by crossing Pggt1b-flox mice (Sjogren AK, 2007) with Villino-Cre mice (deletion of GGTaseI in epithelial cells) or with CD4-Cre mice (deletion of GGTaseI in CD4 + T cells) and do analysis of the evolution of these mice after several models of inflammation-associated colon cancer (AOM / DSS model) or in colitis models.
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