PMID- 7744880 OWN - NLM STAT- MEDLINE DCOM- 19950612 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 270 IP - 20 DP - 1995 May 19 TI - The human leukocyte antigen A2 interferon-stimulated response element consensus sequence binds a nuclear factor required for constitutive expression. PG - 12276-85 AB - Both constitutive and interferon-inducible enhancer-like elements have been identified previously in the promoter of human leukocyte antigen (HLA) class I genes. One of these sites is termed the interferon-stimulated response element (ISRE). We have tested the function of an ISRE consensus sequence in the human HLA class I gene HLA-A2 and confirmed previous studies that showed that the HLA-A2 ISRE consensus sequence does not mediate a response to interferons. However, deletion of the ISRE consensus sequence caused a several-fold reduction in the constitutive expression of the HLA-A2 gene in K562 and Jurkat cells. Mobility shift assays performed with the HLA-A2 ISRE revealed the presence of a constitutive binding protein (ISRE/CBP). This protein binds specifically to the HLA-A2 ISRE sequence, and binding is not efficiently competed by the ISRE sequences of the HLA-B7 or ISG54 genes. Substitution of the HLA-B7 or ISG54 ISRE sequences for the HLA-A2 ISRE sequence caused a severalfold reduction in the constitutive expression of the HLA-A2 gene. Mass determinations showed the ISRE/CBP to be 105 kDa, different than any previously characterized ISRE binding proteins. We propose that ISRE/CBP is a novel positive transcriptional regulatory factor for the HLA-A2 gene that may contribute to the differential expression of HLA-A versus HLA-B genes. FAU - Waring, J F AU - Waring JF AD - Department of Medicine, University of Minnesota, Minneapolis 55455, USA. FAU - Radford, J E AU - Radford JE FAU - Burns, L J AU - Burns LJ FAU - Ginder, G D AU - Ginder GD LA - eng GR - R01-CA45634/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Carrier Proteins) RN - 0 (HLA-A2 Antigen) RN - 0 (HLA-B7 Antigen) RN - 0 (Neoplasm Proteins) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Base Sequence MH - Binding Sites MH - Carrier Proteins/isolation & purification/*metabolism MH - Consensus Sequence MH - *Enhancer Elements, Genetic MH - *Gene Expression Regulation/drug effects MH - Gene Expression Regulation, Neoplastic/drug effects MH - *Genes, MHC Class I MH - HLA-A2 Antigen/*genetics MH - HLA-B7 Antigen/genetics MH - Humans MH - Interferon-gamma/*pharmacology MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology MH - Leukemia-Lymphoma, Adult T-Cell/pathology MH - Molecular Sequence Data MH - Molecular Weight MH - Mutagenesis, Site-Directed MH - Neoplasm Proteins/biosynthesis/genetics MH - Protein Binding MH - Sequence Alignment MH - Tumor Cells, Cultured EDAT- 1995/05/19 00:00 MHDA- 1995/05/19 00:01 CRDT- 1995/05/19 00:00 PHST- 1995/05/19 00:00 [pubmed] PHST- 1995/05/19 00:01 [medline] PHST- 1995/05/19 00:00 [entrez] AID - S0021-9258(17)47971-3 [pii] AID - 10.1074/jbc.270.20.12276 [doi] PST - ppublish SO - J Biol Chem. 1995 May 19;270(20):12276-85. doi: 10.1074/jbc.270.20.12276.