INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Functional characterization of Trypanosoma brucei ubiquiting conjugating enzyme CDC34
Autor/es:
ROJAS F, MONERAT S., BÚA J, MOTTRAM J.C., TÉLLEZ-IÑÓN, MT.
Lugar:
San Miguel de Tucumán, 10-13 Noviembre, Argentina.
Reunión:
Congreso; XLV Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology (SAIB).; 2009
Institución organizadora:
Sociedada Argentina de Investigación en Bioquímica y Biología Molecular, SAIB
Resumen:
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The UPS (ubiquitinproteasome system) is a fundamental
regulatory pathway for controlling protein stability that underlies many
cellular processes, such as signaling and cell cycle progression. In response
to particular signals, specific regulatory proteins are tagged with a chain of
ubiquitin molecules through the action of an enzymatic cascade composed of an
E1 ubiquitin activating enzyme, an E2 ubiquitin conjugating enzyme (Ubc), and
an E3 ubiquitin ligase. E3s are responsible for binding substrates and for bringing
substrates into the proximity of a ubiquitin-charged E2, which then transfers
ubiquitin to the substrate and to the ensuing ubiquitin chain in a processive
reaction. The importance of the UPS for cell cycle progression is exemplified
by the central role of the ubiquitin-conjugating enzyme Cdc34, which
co-operates with the SCF E3 ligase to regulate the levels of key cell cycle
regulators. A major substrate of the Cdc34SCF complex in S. cerevisiae is the
CDK (cyclin-dependent kinase) inhibitor Sic1, whose precise ubiquitin-mediated
proteolysis is necessary for the G1S-phase cell cycle transition. We are
investigating the functional role of CDC34 in T. brucei using RNAi and dominant
negative overexpression. We show that RNAi of CDC34 in bloodstream form trypanosomes
results in an in vitro growth defect with defects in cytokinesis furrow
ingression. Cellular localization, RNAI interference induction in vivo and 2D-DIGE analysis are
currently being investigated.