The effect of proteasome inhibition on the generation of the human leukocyte antigen (HLA) peptidome.

Détails

ID Serval
serval:BIB_C8CA6839C5D9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The effect of proteasome inhibition on the generation of the human leukocyte antigen (HLA) peptidome.
Périodique
Molecular & cellular proteomics
Auteur(s)
Milner E., Gutter-Kapon L., Bassani-Strenberg M., Barnea E., Beer I., Admon A.
ISSN
1535-9484 (Electronic)
ISSN-L
1535-9476
Statut éditorial
Publié
Date de publication
07/2013
Peer-reviewed
Oui
Volume
12
Numéro
7
Pages
1853-1864
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The Major histocompatibility complex (MHC) class I peptidome is thought to be generated mostly through proteasomal degradation of cellular proteins, a notion that is based on the alterations in presentation of selected peptides following proteasome inhibition. We evaluated the effects of proteasome inhibitors, epoxomicin and bortezomib, on human cultured cancer cells. Because the inhibitors did not reduce the level of presentation of the cell surface human leukocyte antigen (HLA) molecules, we followed their effects on the rates of synthesis of both HLA peptidome and proteome of the cells, using dynamic stable isotope labeling in tissue culture (dynamic-SILAC). The inhibitors reduced the rates of synthesis of most cellular proteins and HLA peptides, yet the synthesis rates of some of the proteins and HLA peptides was not decreased by the inhibitors and of some even increased. Therefore, we concluded that the inhibitors affected the production of the HLA peptidome in a complex manner, including modulation of the synthesis rates of the source proteins of the HLA peptides, in addition to their effect on their degradation. The collected data may suggest that the current reliance on proteasome inhibition may overestimate the centrality of the proteasome in the generation of the MHC peptidome. It is therefore suggested that the relative contribution of the proteasomal and nonproteasomal pathways to the production of the MHC peptidome should be revaluated in accordance with the inhibitors effects on the synthesis rates of the source proteins of the MHC peptides.
Mots-clé
Boronic Acids/pharmacology, Bortezomib, Cell Proliferation/drug effects, Cell Survival/drug effects, Histocompatibility Antigens Class I/metabolism, Humans, MCF-7 Cells, Oligopeptides/pharmacology, Peptides/metabolism, Proteasome Inhibitors/pharmacology, Proteome, Pyrazines/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/07/2019 17:37
Dernière modification de la notice
21/08/2019 6:35
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