Abstract
Glycosylation is one of the essential modifications of proteins and lipids. It is carried out mainly in the endoplasmic reticulum and Golgi apparatus, and requires a specific molecular machinery associating several hundreds of glycosyltransferases, glycosidases, transporters and regulating proteins. Modifications of glycosylation are found in numerous diseases, notably in cancers. All types of glycosylation can be affected and this leads to dysfunctions of cellular metabolism. In this review, we present the current knowledge on the regulation of glycosylation mechanisms and illustrate how the alteration of these regulatory mechanisms can lead to abnormal protein and lipid glycosylation, and take part in the development of cancers.
Highlights
Modifications of glycosylation are found in numerous diseases, notably in cancers
All types of glycosylation can be affected and this leads to dysfunctions of cellular metabolism
We present the current knowledge on the regulation of glycosylation mechanisms and illustrate how the alteration of these regulatory mechanisms can lead to abnormal protein and lipid glycosylation, and take part in the development of cancers. ‡
Summary
Un premier élément important à considérer est qu’il n’existe évidemment pas, per se, de gènes codant ces structures glycanniques, contrairement aux protéines. Pour les N-glycoprotéines, et uniquement pour ces dernières, un véritable contrôle qualité, fondé sur la structure même de la chaîne glycannique, s’effectue dans le réticulum endoplasmique (RE). Dans certains cancers (poumon, sein), l’expression d’ERK8 est réduite, diminuant les capacités de relocalisation des enzymes, ce qui affecte directement la quantité de structures O-glycanniques produites [18]. Ces quelques exemples illustrent l’importance d’un maintien de la localisation subcellulaire et de la topographie de certains acteurs dans le processus de glycosylation. La glycosylation étant une suite de réactions enzymatiques, l’environnement ionique de chaque saccule est en effet un élément clé pour l’élaboration d’une structure glycannique correcte. La modulation et le maintien de ces gradients ioniques dans la voie de sécrétion golgienne sont donc primordiaux pour la glycosylation [23] (Figure 1B). La compréhension des mécanismes impliqués dans la production de ces gradients et permettant leur maintien reste très fragmentaire
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