Cell signaling mechanism of Trypanosoma in response to nutritional alterations and genotoxic agents

Abstract

The signaling pathways that control translation initiation/elongation and the transcription and replication arrest after different types of stress in eukaryotes depend on the activation/inactivation of protein kinases. Among them are the kinases that phosphorylate the eukaryotic initiation factor 2 (eIF2), kinases known as TOR, and the phosphorylation of the protein known as eiFSA, characterized as a translation elongation factor. Replication and transcription arrest occurs after histone phosphorylation and RNA polymerase II dephosphorylation followed by chromatin remodeling and DNA repair promoted by single strand DNA-binding proteins and histone chaperones. In this project we intend to identify some of the signaling mechanisms involved in the growth related to the translation control and DNA metabolism after nutritional stresses in protozoan parasites of Trypanosoma species. We will investigate the role of these signaling pathways in the differentiation and growth by detecting alterations in e phosphorylation state and by promoting alterations in the phosphorylation sites. In parallel, we will investigate some components of the chromatin remodeling and the roIe of the differential phosphorylation of the unique carboxy-terminal domain of the large subunit of the RNA Polymerase II in Trypanosoma. These studies will allow us to understand how these parasites deal with environmental changes, which are the basis for their survival in their hosts. This information will be useful to identify new drug targets to treat diseases caused by these types of parasites. (AU)