Abstract: |
Patients with renal and colon cancer frequently develop IgG autoantibodies toward the NY-CO-38/PDZ-73 antigen, a protein of 652 amino acids (73 kDa) which contains three copies of the PDZ protein-protein interaction domain. The gene encoding PDZ-73 mapped to chromosome 11p15.4- p15.1. Additional tissue-specific isoforms were identified: PDZ-45, which lacks the third PDZ domain and the putative PEST protein degradation motif, is expressed in kidney, colon, small intestine, brain and testis; PDZ-54 and PDZ-59, which also lack the third PDZ domains, have unique carboxyl terminal amino acids and are expressed in brain, kidney, bladder, colon cancer and renal cancer; and a putative PDZ-37 isoform, containing only the third PDZ domain, that is expressed in the central nervous system. Immunohistochemical staining with anti-PDZ 73 monoclonal antibodies showed strong cytoplasmic reactivity in epithelial cells of the small intestine, colon and kidney tubules, with a prominent apical staining pattern in cells of the small intestine. The reactivity pattern of the antibodies with various tissues correlated with the mRNA expression pattern of the PDZ-45 isoform. The existence of multiple PDZ-73 isoforms with variations in tissue distribution, PDZ domains, protein degradation sequences and carboxyl terminal structure indicate that these isoforms have distinct tissue-specific functions. |
Keywords: |
immunohistochemistry; protein expression; unclassified drug; human cell; protein domain; carboxy terminal sequence; protein degradation; protein protein interaction; colonic neoplasms; kidney neoplasms; cloning, molecular; dna; amino acid sequence; molecular sequence data; antigen; brain; rna, messenger; colon cancer; nucleotide sequence; carrier proteins; adaptor proteins, signal transducing; base sequence; dna sequence; autoantibody; intestine, small; testis; protein isoforms; immunoglobulin g antibody; chromosome mapping; dna, complementary; tissue specificity; chromosome 11p; pdz domain; humans; human; male; priority journal; article; 11p15.4-p15.1; isoform expression; ny-co-38 antigen; serological expression cloning; protein pdz 73
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