Web of Science: 2 citations, Scopus: 2 citations, Google Scholar: citations,
The ubiquitin-conjugating enzyme CDC34 is essential for cytokinesis in contrast to putative subunits of a SCF complex in Trypanosoma brucei
Rojas, Federico (Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (Buenos Aires))
Koszela, Joanna (University of Edinburgh Medical School. College of Medicine and Veterinary Medicine)
Búa, Jacqueline E. (Instituto Nacional de Diagnostico e Investigacion de la Enfermedad de Chagas Dr. Mario Fatala Chaben)
Llorente, Briardo (Centre de Recerca en Agrigenòmica)
Burchmore, Richard Js (University of Glasgow. Institute of Infection, Immunity and Inflammation)
Auer, Manfred (University of Edinburgh Medical School. College of Medicine and Veterinary Medicine)
Mottram, Jeremy C. (University of York. Department of Biology)
Téllez-Iñón, María Teresa (Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (Buenos Aires))

Date: 2017
Abstract: The ubiquitin-proteasome system is a post-translational regulatory pathway for controlling protein stability and activity that underlies many fundamental cellular processes, including cell cycle progression. Target proteins are tagged with ubiquitin molecules through the action of an enzymatic cascade composed of E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, and E3 ubiquitin ligases. One of the E3 ligases known to be responsible for the ubiquitination of cell cycle regulators in eukaryotes is the SKP1-CUL1-F-box complex (SCFC). In this work, we identified and studied the function of homologue proteins of the SCFC in the life cycle of Trypanosoma brucei, the causal agent of the African sleeping sickness. Depletion of trypanosomal SCFC components TbRBX1, TbSKP1, and TbCDC34 by RNAi resulted in decreased growth rate and contrasting cell cycle abnormalities for both procyclic (PCF) and bloodstream (BSF) forms. Depletion of TbRBX1 in PCF cells interfered with kinetoplast replication, whilst depletion of TbSKP1 arrested PCF and BSF cells in the G1/S transition. Silencing of TbCDC34 in BSF cells resulted in a block in cytokinesis and caused rapid clearance of parasites from infected mice. We also show that TbCDC34 is able to conjugate ubiquitin in vitro and in vivo, and that its activity is necessary for T. brucei infection progression in mice. This study reveals that different components of a putative SCFC have contrasting phenotypes once depleted from the cells, and that TbCDC34 is essential for trypanosome replication, making it a potential target for therapeutic intervention.
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Published in: PLoS neglected tropical diseases, Vol. 11 Núm. 6 (2017) , e0005626, ISSN 1935-2727

DOI: 10.1371/journal.pntd.0005626
PMID: 28609481


22 p, 8.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Experimental sciences > CRAG (Centre for Research in Agricultural Genomics)
Articles > Research articles
Articles > Published articles

 Record created 2018-07-12, last modified 2018-10-20



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