CONICET | Buscador de Institutos y Recursos Humanos

Trypanosoma cruzi, the etiologic agent of Chagasdisease, is a protozoan parasite with a life cycle that alternates betweenreplicative and non-replicative forms, but the components and mechanisms thatregulate its cell cycle are poorly described. In higher eukaryotes, cyclins areproteins that activate cyclin-dependent kinases (CDKs), by associating withthem along the different stages of the cell cycle. These cyclin-CDKs complexesexert their role as major modulators of the cell cycle by phosphorylatingspecific substrates. For the correct progression of the cell cycle, the mechanisms that regulate theactivity of cyclins and their associated CDKs are diverse and must becontrolled precisely. Different types of cyclins are involved in specificphases of the eukaryotic cell cycle, preferentially activating certain CDKs. Inthis work, we characterized TcCYC6, aputative coding sequence of T. cruziwhich encodes a protein with homology to mitotic cyclins. The overexpression ofthis sequence, fused to a tag of nine amino acids from influenza virushemagglutinin (TcCYC6-HA), showed tobe detrimental for the proliferation of epimastigotes in axenic culture andaffected the cell cycle progression. Insilico analysis revealed an N-terminal segment similar to the consensussequence of the destruction box, a hallmark for the degradation of severalmitotic cyclins. We experimentally determined that the TcCYC6-HA turnover decreased in the presence of proteasomeinhibitors, suggesting that TcCYC6 degradationoccurs via ubiquitin-proteasome pathway. Theresults obtained in this study provide first evidence that TcCYC6 expression and degradation is finely regulated in T. cruzi.