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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Milner, Elena Gutter-Kapon, Lilach Bassani-Strenberg, Michal Barnea, Eilon Beer, Ilan Admon, Arie
Description	Country affiliation: Israel Author Affiliation: Milner E ( Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.)
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.
File Format	HTM / HTML
ISSN	15359476
e-ISSN	15359484
DOI	10.1074/mcp.M112.026013
Journal	Molecular & Cellular Proteomics
Issue Number	7
Volume Number	12
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2013-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Proteomics Boronic Acids Pharmacology Histocompatibility Antigens Class I Metabolism Peptides Proteasome Inhibitors Pyrazines Bortezomib Cell Proliferation Drug Effects Cell Survival Mcf-7 Cells Oligopeptides Proteome Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Analytical Chemistry Molecular Biology Biochemistry

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