The bacterial-like HslVU protease complex subunits are involved in the control of different cell cycle events in trypanosomatids

Autor: Ndeye-Mathy Kebe, Pierre Portales, Jean-François Hernandez, Yvon Sterkers, Lucien Crobu, Patrick Bastien, Olivier Coux, Sabrina Meghamla, Diane-Ethna Mbang-Benet, Christelle Morelle, Michel Pagès
Přispěvatelé: Biologie, Génétique et Pathologie des Pathogènes Eucaryotes (MIVEGEC-BioGEPPE), Pathogènes, Environnement, Santé Humaine (EPATH), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Adaptations Physiologiques à l'Exercice et Réadaptation à l'effort - UR UPJV 3300 (APERE), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Biologie moléculaire, biologie cellulaire et biodivesité des protozoaires parasites (FRE3013), Université Montpellier 1 (UM1), University Hospital of Montpellier
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Proteasome Endopeptidase Complex
Trypanosoma
Veterinary (miscellaneous)
Protein subunit
Recombinant Fusion Proteins
[SDV]Life Sciences [q-bio]
Trypanosoma brucei brucei
Protozoan Proteins
Drug target
HslVU
MESH: Celle Cycle/genetics
Endopeptidase clp/genetics
Escherichia poli Proteins/genetics
Leishmania major/genetics
Mitochondria/genetics
Protozoan
RNAinterference
parasitic diseases
Escherichia coli
Leishmania major
Gene
Leishmania
Life Cycle Stages
biology
Sequence Homology
Amino Acid
Proteasome
Escherichia coli Proteins
Cell Cycle
Endopeptidase Clp
biology.organism_classification
Subcellular localization
3. Good health
Cell biology
Mitochondria
Isoenzymes
Protein Subunits
Infectious Diseases
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Gene Expression Regulation
Insect Science
biology.protein
Parasitology
Zdroj: Acta Tropica
Acta Tropica, Elsevier, 2014, 131, pp.22-31. ⟨10.1016/j.actatropica.2013.11.017⟩
ISSN: 0001-706X
Popis: International audience; The trypanosomatid parasites Leishmania and Trypanosoma are responsible for the most important WHO-designated neglected tropical diseases, for which the need for cost-effective new drugs is urgent. In addition to the classical eukaryotic 20S and 26S proteasomes, these unconventional eukaryotes possess a bacterial-like protease complex, HslVU, made of proteolytic (HslV) and regulatory (HslU) subunits. In trypanosomatids, two paralogous genes are co-expressed: HslU1 and HslU2. Conflicting reports have been published with respect to subcellular localization, functional redundancy and putative roles of the different subunits of this complex in trypanosomatids. Here, we definitively established the mitochondrial localization of HslVU in L. major procyclic promastigotes and of HslV in T. brucei bloodstream trypomastigotes, the latter being the form responsible for the disease in the mammalian host. Moreover, our data demonstrate for the first time the essential nature of HslVU in the bloodstream trypomastigotes of T. brucei, in spite of mitochondrial repression at this stage. Interestingly, our work also allows distinguishing a specific role for the different members of the complex, as HslV and HslU1 appear to be involved in the control of different cell cycle events. Finally, these data validate HslVU as a promising drug target against these parasitic diseases of wide medical and economical importance.
Databáze: OpenAIRE
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