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:
<!-- /* Font Definitions */ @font-face {font-family:Tahoma; panose-1:2 11 6 4 3 5 4 4 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:1627421319 -2147483648 8 0 66047 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-GB; mso-fareast-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> The UPS (ubiquitin–proteasome 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 Cdc34–SCF complex in S. cerevisiae is the CDK (cyclin-dependent kinase) inhibitor Sic1, whose precise ubiquitin-mediated proteolysis is necessary for the G1–S-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.