Transcriptional regulation of human papillomavirus type 16 LCR by different C/EBPbeta isoforms.
During genital human papillomavirus (HPV) infection several cytokines are released, such as interleukin-1 (IL-1), tumor necrosis factoralpha (TNFalpha), IL-6, and IL-8. These cytokines may play a role in the immune surveillance against viral infection. Two of these cytokines, IL-1 and TNFalpha, suppress the transcription of the HPV16 early genes. CAATT/ enhancer binding protein, (C/EBPbeta), which is activated by IL-1 and TNFalpha, has been suggested to act as a mediator of this transcriptional downregulation. C/EBPbeta contains three different translation initiation sites that can lead probably by leaky ribosome scanning to the generation of three isoforms of C/EBPbeta, namely full-length C/EBPbeta, liver enriched transcriptional activator protein (LAP), and liver enriched inhibitory protein (LIP). When transiently expressed in C33A and HeLa cells, the first two C/EBPbeta isoforms activate the HPV16 long control region (LCR). LIP, which acts as an antagonist of C/EBPbeta, represses the HPV16 LCR activity. Our observation that treatment of HeLa cells with IL-1 leads to induction of LIP supports the hypothesis that the LCR downregulation by IL-1 is mediated by LIP.
Struyk
L
L
Department of Virology, Academic Medical Center, University of Amsterdam, The Netherlands.
van der Meijden
E
E
Minnaar
R
R
Fontaine
V
V
Meijer
I
I
ter Schegget
J
J
D022762:CCAAT-Enhancer-Binding Proteins; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms