Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s).
During human cytomegalovirus (HCMV) infection, a rapid increase in AP-1 activity is detected. In this study, activation of transcription from promoters containing AP-1-binding sites by the IE1 protein of HCMV was examined. In transient transfection assays with reporter plasmids, it was found that IE1 strongly induced AP-1-driven transcription. Cells stably expressing IE1 also showed higher levels of AP-1 activity than did control cells. IE1 expression did not raise levels of c-jun and c-fos RNA, as determined by quantitative RT-PCR. AP-1 induction by IE1 was blocked efficiently by protein kinase inhibitors in a cell type-dependent manner; for example, by staurosporine in the human microglial cell line U373MG and by H7 in the human promonocytic cell line U937. IE1-driven activation of AP-1 was increased dramatically by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1). The results of this study indicate that IE1 activates AP-1 at the post-transcriptional level and that MEKK1 may play an important role in this process.
Kim
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Yu
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Lee
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Ohno
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Yim
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J
Kim
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Kang
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HS
D002478:Cells, Cultured; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D048728:MAP Kinase Kinase Kinase 1; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation; D014764:Viral Proteins
C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D018808:Transcription Factor AP-1; D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human