RAP80/UIMC1 as cancer-associated antigen: alternative splice variants and their immunogenicity.
We have identified RAP80/UIMC1, the protein highly expressed in testis, as a new cancer-associated antigen. Sera from 5% to 10% of patients with different types of cancer contain specific antibodies to RAP80/UIMC1. In order to investigate the possible reasons for RAP80/UIMC1 immunogenicity, we characterized its numerous splice isoforms and mapped immunogenic regions of the protein. The majority of RAP80/UIMC1 transcripts was detected both in normal tissues and in colon tumors. There are several RAP80/UIMC1 isoforms that are predominantly expressed in testis, however we did not observe elevated expression of these transcripts in tumors from seropositive patients. We mapped the major immunogenic region of RAP80/UIMC1 to the central part of the protein encoded by exon 9 which is present in a number of ubiquitous splice forms. Thus, based on our data, autoreactivity to RAP80/UIMC1 is related to reasons other than overexpression or tumor-specific splicing.
Shebzukhov
Yuriy V
YV
Department of Molecular Immunology, Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobjovy Gory, Moscow 119899, Russia.
Koroleva
Ekaterina P
EP
Khlgatian
Svetlana V
SV
Belousov
Pavel V
PV
Sazykin
Alexey Y
AY
Kadachigova
Tatiana S
TS
Pomerantseva
Ekaterina A
EA
Lagarkova
Maria A
MA
Nedospasov
Sergei A
SA
Kuprash
Dmitry V
DV
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D056488:Histone Chaperones; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology*; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018985:Epitopes, B-Lymphocyte; D056488:Histone Chaperones; D009687:Nuclear Proteins; C466234:UIMC1 protein, human