title: Characterization of TcCYC6 from Trypanosoma cruzi, a gene with homology to mitotic cyclins.
abstract: Trypanosoma cruzi, the etiologic agent of Chagas disease, is a protozoan parasite with a life cycle that alternates between replicative and non-replicative forms, but the components and mechanisms that regulate its cell cycle are 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 their role as major modulators of the cell cycle by phosphorylating specific substrates. For the correct progression of the cell cycle, the mechanisms that regulate the activity of cyclins and their associated CDKs are diverse and must be controlled precisely. Different types of cyclins are involved in specific phases of the eukaryotic cell cycle, preferentially activating certain CDKs. In this work, we characterized TcCYC6, a putative coding sequence of 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 detrimental for the proliferation of epimastigotes in axenic culture and affected the cell cycle progression. In silico analysis revealed an N-terminal segment similar to the consensus sequence of the destruction box, a hallmark for the degradation of several mitotic cyclins. We experimentally determined that the TcCYC6-HA turnover decreased in the presence 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 finely regulated in T. cruzi.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. H.N. Torres", INGEBI-CONICET, Vuelta de Obligado 2490 (C1428ADN), Buenos Aires, Argentina.
authors.forename: María Agostina
authors.initials: MA
authors.lastname: Di Renzo
authors.affiliation: Instituto de Investigaciones Biotecnológicas IIB-INTECH, Universidad Nacional de San Martín - CONICET, Buenos Aires, Argentina.
authors.forename: Marc
authors.initials: M
authors.lastname: Laverrière
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Rua Pedro de Toledo 669 6andar (SP 04039-032), São Paulo, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Schenkman
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. H.N. Torres", INGEBI-CONICET, Vuelta de Obligado 2490 (C1428ADN), Buenos Aires, Argentina.
authors.forename: Diana Patricia
authors.initials: DP
authors.lastname: Wehrendt
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. H.N. Torres", INGEBI-CONICET, Vuelta de Obligado 2490 (C1428ADN), Buenos Aires, Argentina.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Tellez-Iñón
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. H.N. Torres", INGEBI-CONICET, Vuelta de Obligado 2490 (C1428ADN), Buenos Aires, Argentina. Electronic address: mariana.potenza@ingebi.conicet.gov.ar.
authors.forename: Mariana
authors.initials: M
authors.lastname: Potenza
mesh_terms: D000818:Animals; D002453:Cell Cycle; D014355:Chagas Disease / Q000469:parasitology*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006388:Hemagglutinins / Q000235:genetics / Q000378:metabolism; D009975:Orthomyxoviridae / Q000235:genetics; D010766:Phosphorylation; D059748:Proteolysis; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D014349:Trypanosoma cruzi / Q000166:cytology / Q000235:genetics* / Q000378:metabolism
chemical_list: D016213:Cyclins; D006388:Hemagglutinins; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D018844:Cyclin-Dependent Kinases
keywords: Cell cycle; Cyclin; Destruction box; Trypanosoma cruzi