Prolil-isomerización dependiente de fosforilación en Trypanosoma cruzi”.

ERBEN E D; DAUM S; COLOMBO M. I.,; ROMANO P; TÉLLEZ-IÑÓN M T

Huerta Grande, Córdoba

Congreso; Reunión Anual Sociedad Arg. de Protozoología y Enfermedades Parasitarias; 2006

Sociedad Argentina de Protozoología

Eukaryotic cells require ubiquitin mediated protein degradation to maintain proper cell cycle progression. Proteins typically are marked for proteolytic degradation by attachment of multiubiquitin chains. This process is initiated by an ubiquitin-activating enzyme (E1), which activates ubiquitin by adenylation and becomes linked to it via a thiolester bond. Ubiquitin then is transferred to an ubiquitin-conjugating enzyme, E2. Whereas E2 can attach ubiquitin directly to lysine residues in a substrate, most physiological ubiquitination reactions require an ubiquitin ligase, or E3. A multi-ubiquitin chain is generated, targeting the protein for degradation by the 26S proteasome. The SCF-complex specifically recognize phosphorylated substrates so that the regulation is devolved to the level of substrate phosphorylation, which is often CDK dependent. In order to gain insights into the regulation of T.cruzi cell cycle, we looked further for the presence of key regulatory molecules known to be implicated in the regulation of the mammalian cell cycle. To further address the function of the SCF complex in trypanosomes, we used RNA interference to downregulate the proteins in T. brucei. So far, our studies revealed that TbRbx1 is encoded by an essential gene. Experiments are in progress to study the role of this molecule in the protein degradation process and in the cell cycle. Supported by FONCYT, CONICET, UBA.