PMID- 23538226
OWN - NLM
STAT- MEDLINE
DCOM- 20140128
LR  - 20211021
IS  - 1535-9484 (Electronic)
IS  - 1535-9476 (Print)
IS  - 1535-9476 (Linking)
VI  - 12
IP  - 7
DP  - 2013 Jul
TI  - The effect of proteasome inhibition on the generation of the human leukocyte 
      antigen (HLA) peptidome.
PG  - 1853-64
LID - 10.1074/mcp.M112.026013 [doi]
AB  - 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.
FAU - Milner, Elena
AU  - Milner E
AD  - Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
FAU - Gutter-Kapon, Lilach
AU  - Gutter-Kapon L
FAU - Bassani-Strenberg, Michal
AU  - Bassani-Strenberg M
FAU - Barnea, Eilon
AU  - Barnea E
FAU - Beer, Ilan
AU  - Beer I
FAU - Admon, Arie
AU  - Admon A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130328
PL  - United States
TA  - Mol Cell Proteomics
JT  - Molecular & cellular proteomics : MCP
JID - 101125647
RN  - 0 (Boronic Acids)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptides)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Proteome)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - Y0900I3U8U (epoxomicin)
SB  - IM
MH  - Boronic Acids/*pharmacology
MH  - Bortezomib
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - MCF-7 Cells
MH  - Oligopeptides/pharmacology
MH  - Peptides/*metabolism
MH  - Proteasome Inhibitors/*pharmacology
MH  - Proteome
MH  - Pyrazines/*pharmacology
PMC - PMC3708171
EDAT- 2013/03/30 06:00
MHDA- 2014/01/29 06:00
PMCR- 2014/07/01
CRDT- 2013/03/30 06:00
PHST- 2013/03/30 06:00 [entrez]
PHST- 2013/03/30 06:00 [pubmed]
PHST- 2014/01/29 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - S1535-9476(20)32555-X [pii]
AID - M112.026013 [pii]
AID - 10.1074/mcp.M112.026013 [doi]
PST - ppublish
SO  - Mol Cell Proteomics. 2013 Jul;12(7):1853-64. doi: 10.1074/mcp.M112.026013. Epub 
      2013 Mar 28.