Résumés
Résumé
Le protéasome est la principale machinerie protéolytique de la cellule. Il est impliqué dans toutes les grandes fonctions et décisions cellulaires. On a longtemps pensé que presque tous ses substrats devaient préalablement être ubiquitinylés. On a aussi longtemps considéré que l’ubiquitinylation et la dégradation étaient deux mécanismes découplés, et que le recrutement des conjugués ubiquitine s’effectuait directement par des sous-unités spécialisées du protéasome. La littérature récente remet en cause cette vue simplifiée. Elle suggère ainsi que la fraction des protéines hydrolysées par le protéasome, indépendamment de toute ubiquitinylation, a largement été sous-estimée, et que la reconnaissance des protéines ubiquitinylées fait intervenir des systèmes d’adressage complexes. Par ailleurs, elle indique un ordre d’organisation supérieur pour la voie ubiquitine/protéasome, une fraction du protéasome et des enzyme d’ubiquitinylation étant engagée dans des complexes supramoléculaires. Enfin, la dégradation protéasomique est altérée dans de nombreuses situations pathologiques. Elle constitue donc une cible thérapeutique dont les premières applications commencent à émerger.
Summary
The proteasome is the main intracellular proteolytic machinery. It is involved in all major cellular functions and decisions. It has long been thought that prior ubiquitinylation of almost all of its substrates was necessary for degradation. It has also long been considered that ubiquitinylation and degradation were two uncoupled mechanisms and that the recruitment of ubiquitinylated species was only performed by specialized subunits of the proteasome. The recent literature questions this simplified view. It also suggests that, on the one hand, the fraction of proteins hydrolyzed by the proteasome independently of their ubiquitinylation has largely been underestimated and, on the other hand, that the recognition of ubiquitinylated proteins involves complex addressing systems. Furthermore, it indicates a higher order structuration of the ubiquitin/proteasome pathway, a fraction of the proteasome and of ubiquitinylation enzymes being engaged in supramolecular complexes. Finally, proteasomal degradation is altered in a number of pathological situations. It, thus, constitutes a therapeutic target and the first applications are emerging.
Parties annexes
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