PMID- 19917673
OWN - NLM
STAT- MEDLINE
DCOM- 20100511
LR  - 20131121
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 24
IP  - 3
DP  - 2010 Mar
TI  - Differential arginine methylation of the G-protein pathway suppressor GPS-2 
      recognized by tumor-specific T cells in melanoma.
PG  - 937-46
LID - 10.1096/fj.09-136283 [doi]
AB  - The aim of the study was to identify as potential therapeutic targets specific 
      molecular alterations in tumor cells recognized by the immune system. To identify 
      such targets, we analyzed the human leukocyte antigen (HLA) peptidomes of human 
      melanoma cells by 2-dimensional nano-HPLC/mass spectrometry and tested the 
      immunological significance of the peptides by ex vivo ELISpot assays with 
      lymphocytes from melanoma patients. The peptide SQNPRFYHK was identified as 
      derived from the regulator of the nuclear corepressor complex (NCoR) G-protein 
      pathway suppressor 2 (GPS-2) and to be differentially unmethylated, 
      monomethylated or asymmetrically dimethylated at the arginine. The methylation 
      state was specifically recognized by the immune system in that only the 
      monomethylated variant induced T-cell responses and significantly stronger 
      responses in patients than in healthy controls. The methylations were confirmed 
      with synthetic analogues and in vitro radiolabeling assays with recombinant GPS-2 
      and synthetic peptides. The immunity of the 3 variants of GPS-2 was tested in 
      T-cell assays with T lymphocytes of melanoma patients compared with healthy 
      donors. The results show for the first time that GPS-2 is differentially 
      methylated at a site that lacks known methylation motifs and that the methylation 
      state is detected by the immune system.-Jarmalavicius, S., Trefzer, U., Walden, 
      P. Differential arginine methylation of the G-protein pathway suppressor GPS-2 
      recognized by tumor-specific T cells in melanoma.
FAU - Jarmalavicius, Saulius
AU  - Jarmalavicius S
AD  - Department of Dermatology, Charite-Universitatsmedizin Berlin, Humboldt 
      University, Chariteplatz 1, 10117 Berlin, Germany. peter.walden@charite.de
FAU - Trefzer, Uwe
AU  - Trefzer U
FAU - Walden, Peter
AU  - Walden P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091116
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (GPS2 protein, human)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A11 Antigen)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Arginine/*metabolism
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid
MH  - HLA-A Antigens/metabolism
MH  - HLA-A11 Antigen
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/immunology/*metabolism
MH  - Leukocytes, Mononuclear/immunology/metabolism
MH  - Mass Spectrometry
MH  - Melanoma/*immunology/*metabolism
MH  - Methylation
MH  - Protein Binding
MH  - Recombinant Proteins/genetics/*metabolism
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
MH  - T-Lymphocytes/immunology/*metabolism
EDAT- 2009/11/18 06:00
MHDA- 2010/05/12 06:00
CRDT- 2009/11/18 06:00
PHST- 2009/11/18 06:00 [entrez]
PHST- 2009/11/18 06:00 [pubmed]
PHST- 2010/05/12 06:00 [medline]
AID - fj.09-136283 [pii]
AID - 10.1096/fj.09-136283 [doi]
PST - ppublish
SO  - FASEB J. 2010 Mar;24(3):937-46. doi: 10.1096/fj.09-136283. Epub 2009 Nov 16.