PMID- 11119603 OWN - NLM STAT- MEDLINE DCOM- 20010104 LR - 20181130 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 75 IP - 1 DP - 2001 Jan TI - Interferon regulatory factor 7 mediates activation of Tap-2 by Epstein-Barr virus latent membrane protein 1. PG - 341-50 AB - Transporter associated with antigen processing 2 (Tap-2) is responsible for ATP-dependent transport of peptides from the cytosol to the endoplasmic reticulum, where peptides bind to newly synthesized human leukocyte antigen (HLA) class I molecules, which are essential for cellular immune responses. Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) has been shown to induce the expression of Tap-2. In this study, the induction of endogenous Tap-2 by LMP-1 is shown to be associated with and requires the expression of interferon regulatory factor 7 (IRF-7). In DG75 Burkitt's lymphoma (BL) cells, in which LMP-1 induces the expression of IRF-7, LMP-1 induced endogenous Tap-2, and ectopic expression of IRF-7 could enhance the induction. In Akata BL cells, in which LMP-1 could not induce IRF-7, LMP-1 could not induce Tap-2. Addition of IRF-7, which complements the defect in Akata cells, could stimulate the expression of Tap-2. Furthermore, LMP-1 and IRF-7A but not other IRF-7 splicing variants could activate endogenous Tap-2. A Tap-2 promoter reporter construct could be activated by the overexpression of IRF-7A. The activation could be specifically enhanced by LMP-1 and was dependent on an intact interferon-stimulated response element (ISRE) present in the Tap-2 promoter. Also, IRF-7 can bind to the Tap-2 promoter under physiological conditions in vivo, as shown by formaldehyde cross-linking, as well as to the Tap-2 ISRE in vitro, as shown by gel mobility shift assays. Furthermore, LMP-1 facilitates the phosphorylation and nuclear translocation of IRF-7. These data point to the role of IRF-7 as a secondary mediator of LMP-1-activated signal transduction for Tap-2 as follows: LMP-1 stimulates the expression of IRF-7 and facilitates its phosphorylation and nuclear translocation, and then the activated IRF-7 mediates the activation of the cellular Tap-2 gene. The induction of Tap-2 by IRF-7 and LMP-1 may have an important implication for the immune response to EBV and its persistence in vivo. FAU - Zhang, L AU - Zhang L AD - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7265, USA. luzhang@med.unc.edu FAU - Pagano, J S AU - Pagano JS LA - eng GR - P01 CA019014/CA/NCI NIH HHS/United States GR - AI 42372-01/AI/NIAID NIH HHS/United States GR - CA 19014/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 3) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (Cytoskeletal Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (IRF7 protein, human) RN - 0 (Interferon Regulatory Factor-7) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (LIM Domain Proteins) RN - 0 (PDLIM7 protein, human) RN - 145892-13-3 (TAP2 protein, human) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 3 MH - ATP-Binding Cassette Transporters/*genetics MH - Adaptor Proteins, Signal Transducing MH - Carrier Proteins/analysis/*physiology MH - Cell Nucleus/metabolism MH - Cytoskeletal Proteins MH - DNA-Binding Proteins/analysis/*physiology MH - *Gene Expression Regulation MH - Humans MH - Interferon Regulatory Factor-7 MH - Intracellular Signaling Peptides and Proteins MH - LIM Domain Proteins MH - Phosphorylation MH - Promoter Regions, Genetic PMC - PMC113927 EDAT- 2000/12/19 11:00 MHDA- 2001/02/28 10:01 PMCR- 2001/01/01 CRDT- 2000/12/19 11:00 PHST- 2000/12/19 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/12/19 11:00 [entrez] PHST- 2001/01/01 00:00 [pmc-release] AID - 1052 [pii] AID - 10.1128/JVI.75.1.341-350.2001 [doi] PST - ppublish SO - J Virol. 2001 Jan;75(1):341-50. doi: 10.1128/JVI.75.1.341-350.2001.