Regulation of human beta 2-microglobulin transactivation in hematopoietic cells.
beta(2)-Microglobulin (beta(2)m) is a chaperone of major histocompatibility complex (MHC) class I (-like) molecules that play a central role in antigen presentation, immunoglobulin transport, and iron metabolism. It is therefore of importance that beta(2)m is adequately expressed in cells that perform these functions, such as hematopoietic cells. In this study, we investigated the transcriptional regulation of beta(2)m in lymphoid and myeloid cell lines through a promoter containing a putative E box, Ets/interferon-stimulated response element (ISRE), and kappa B site. Here we show that upstream stimulatory factor 1 (USF1) and USF2 bind to the E box and regulate beta(2)m transactivation. The nuclear factor kappa B (NF-kappa B) subunits p50 and p65 bind to the kappa B box and p65 transactivates beta(2)m. Interferon regulatory factor 1 (IRF1), IRF2, IRF4, and IRF8, but not PU.1, bind to the Ets/ISRE, and IRF1 and IRF3 are strong transactivators of beta(2)m. Together, all 3 boxes are important for the constitutive and cytokine-induced levels of beta(2)m expression in lymphoid and myeloid cell types. As such, beta(2)m transactivation is under the control of important transcriptional pathways, which are activated during injury, infection, and inflammation.
Gobin
Sam J P
SJ
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Biesta
Paula
P
Van den Elsen
Peter J
PJ
D030161:Avian Proteins; D002461:Cell Line, Transformed / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D050838:Interferon Regulatory Factor-3; D050835:Interferon Regulatory Factors; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism*; D008957:Models, Genetic; D022423:Myeloid Cells / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051720:Upstream Stimulatory Factors; D014947:Wounds and Injuries / Q000235:genetics; D001613:beta 2-Microglobulin / Q000235:genetics*; D000099218:Interferon Regulatory Factor-4
D030161:Avian Proteins; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D050838:Interferon Regulatory Factor-3; D050835:Interferon Regulatory Factors; D000068556:Interferon beta-1a; D016899:Interferon-beta; D007371:Interferon-gamma; D016328:NF-kappa B; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D051720:Upstream Stimulatory Factors; D001613:beta 2-Microglobulin; D000099218:Interferon Regulatory Factor-4; C494257:IRF1 protein, human; C494229:IRF2 protein, human; C494232:IRF3 protein, human; C497181:USF1 protein, human; C497184:USF2 protein, human; C455582:interferon regulatory factor-10, Gallus gallus