Characterization of TcCYC6 from Trypanosoma cruzi, a gene with homology to mitotic cyclins

DI RENZO M. A; LAVERRIÈRE M; SCHENKMAN S; WEHRENDT D. P; TELLEZ-IÑÓN M. T; POTENZA M

PARASITOLOGY INTERNATIONAL

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2015

1383-5769

Trypanosoma cruzi, the etiologic agent of Chagas disease, is a protozoan parasite with a life cycle that alternatesbetween replicative and non-replicative forms, but the components and mechanisms that regulate its cell cycleare poorly described. In higher eukaryotes, cyclins are proteins that activate cyclin-dependent kinases (CDKs),by associating with them along the different stages of the cell cycle. These cyclin?CDK complexes exert theirrole as major modulators of the cell cycle by phosphorylating specific substrates. For the correct progression ofthe cell cycle, the mechanisms that regulate the activity of cyclins and their associated CDKs are diverse andmust be controlled precisely. Different types of cyclins are involved in specific phases of the eukaryotic cellcycle, preferentially activating certain CDKs. In this work, we characterized TcCYC6, a putative coding sequenceof T. cruzi which encodes a protein with homology to mitotic cyclins. The overexpression of this sequence,fused to a tag of nine amino acids from influenza virus hemagglutinin (TcCYC6-HA), showed to be detrimentalfor the proliferation of epimastigotes in axenic culture and affected the cell cycle progression. In silico analysisrevealed an N-terminal segment similar to the consensus sequence of the destruction box, a hallmark for the degradationof several mitotic cyclins.Weexperimentally determined that the TcCYC6-HA turnover decreased in thepresence of proteasome inhibitors, suggesting that TcCYC6 degradation occurs via ubiquitin?proteasome pathway.The results obtained in this study provide first evidence that TcCYC6 expression and degradation are finelyregulated in T. cruzi.