[Metabolic pathways controlled by E3 ligases: an opportunity for therapeutic targeting].
Contrôle des voies métaboliques par les enzymes E3 ligases : une opportunité de ciblage thérapeutique.
E3 ligases
cancers
développements thérapeutiques
inhibiteurs
inhibitors
ligases E3
système ubiquitine-protéasome
therapeutic developments
ubiquitin proteasome system
Journal
Biologie aujourd'hui
ISSN: 2105-0686
Titre abrégé: Biol Aujourdhui
Pays: France
ID NLM: 101544020
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
06
2021
entrez:
16
8
2021
pubmed:
17
8
2021
medline:
26
10
2021
Statut:
ppublish
Résumé
Since its discovery, the Ubiquitin Proteasome System (UPS) has been recognized for its major role in controlling most of the cell's metabolic pathways. In addition to its essential role in the degradation of proteins, it is also involved in the addressing, signaling or repair of DNA, which makes it a key player in cellular homeostasis. Although other control systems exist in the cell, the UPS is often referred to as the conductor. In view of its importance, any dysregulation of the UPS leads to more or less severe disorders for the cell and therefore the body, which accounts for UPS implication in many pathologies (cancer, Alzheimer's disease, Huntington's disease, etc.). UPS is made up of more than 1000 different proteins, the combinations of which allow the fine targeting of virtually all proteins in the body. UPS uses an enzymatic cascade (E1, 2 members; E2 > 35; E3 > 800) which allows the transfer of ubiquitin, a small protein of 8.5 kDa onto the protein to be targeted either for its degradation or to modify its activity. This ubiquitinylation signal is reversible and many deubiquitinylases (DUB, ∼ 80 isoforms) also have an important role. E3 enzymes are the most numerous and their function is to recognize the target protein, which makes them important players in the specific action of UPS. The very nature of E3 and the complexity of their interactions with different partners offer a very broad field of investigation and therefore significant potential for the development of therapeutic approaches. Without being exhaustive, this review illustrates the different strategies that have already been implemented to fight against different pathologies (excluding bacterial or viral infections). Contrôle des voies métaboliques par les enzymes E3 ligases : une opportunité de ciblage thérapeutique. Depuis sa découverte, le Système Ubiquitine Protéasome (UPS) est reconnu pour son rôle majeur dans le contrôle de la plupart des voies métaboliques de la cellule. Outre son rôle primordial dans la dégradation des protéines, il intervient aussi dans l’adressage, la signalisation ou la réparation de l’ADN, ce qui en fait un acteur incontournable de l’homéostasie cellulaire. Bien que d’autres systèmes de contrôles existent dans la cellule, l’UPS est souvent considéré comme le chef d’orchestre. Au vu de son importance, toute dérégulation de l’UPS entraîne des désordres plus ou moins sévères pour la cellule et donc l’organisme. De fait, l’UPS est impliqué dans de nombreuses pathologies (cancer, maladie d’Alzheimer, de Huntington, etc.). L’UPS est composé de plus de 1000 protéines différentes dont les combinaisons permettent le ciblage fin de virtuellement toutes les protéines de l’organisme. L’UPS fait appel à une cascade enzymatique (E1, 2 isoformes ; E2 > 35 isoformes ; E3 > 800 isoformes) qui permet le transfert de l’ubiquitine, une petite protéine de 8,5 kDa, sur la protéine à cibler soit pour sa dégradation, soit pour modifier son activité. Ce signal d’ubiquitinylation est réversible et de nombreuses déubiquitinylases (DUB, ∼ 80 isoformes) jouent aussi un rôle important. Les enzymes E3 sont les plus nombreuses et leur fonction est de reconnaître la protéine cible, ce qui en fait des acteurs importants dans la spécificité d’action de l’UPS. La nature même des E3 et la complexité de leurs interactions avec différents partenaires offrent un champ d’investigation très large et donc des potentialités importantes pour le développement d’approches thérapeutiques. Sans être exhaustive, cette revue illustre les différentes stratégies ayant déjà été mises en œuvre pour lutter contre différentes pathologies (à l’exclusion des infections bactériennes ou virales).
Autres résumés
Type: Publisher
(fre)
Contrôle des voies métaboliques par les enzymes E3 ligases : une opportunité de ciblage thérapeutique.
Identifiants
pubmed: 34397374
doi: 10.1051/jbio/2021006
pii: jbio210006
doi:
Substances chimiques
Ubiquitin
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Review
Langues
fre
Sous-ensembles de citation
IM
Pagination
45-57Informations de copyright
© Société de Biologie, 2021.
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