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

Details

Serval ID
serval:BIB_C8CA6839C5D9
Type
Article: article from journal or magazin.
Collection
Publications
Title
The effect of proteasome inhibition on the generation of the human leukocyte antigen (HLA) peptidome.
Journal
Molecular & cellular proteomics
Author(s)
Milner E., Gutter-Kapon L., Bassani-Strenberg M., Barnea E., Beer I., Admon A.
ISSN
1535-9484 (Electronic)
ISSN-L
1535-9476
Publication state
Published
Issued date
07/2013
Peer-reviewed
Oui
Volume
12
Number
7
Pages
1853-1864
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
26/07/2019 16:37
Last modification date
21/08/2019 5:35
Usage data