Transcriptional regulation of human papillomavirus type 16 LCR by different C/EBPβ isoforms

✍ Scribed by Linda Struyk; Els van der Meijden; René Minnaar; Véronique Fontaine; Ingeborg Meijer; Jan ter Schegget

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 206 KB
• Volume: 28
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(200005)28:1<42::aid-mc6>3.0.co;2-8

✦ Synopsis

During genital human papillomavirus (HPV) infection several cytokines are released, such as interleukin-1 (IL-1), tumor necrosis factora (TNFa), 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 TNFa, suppress the transcription of the HPV16 early genes. CAATT/ enhancer binding proteinb (C/EBPb), which is activated by IL-1 and TNFa, has been suggested to act as a mediator of this transcriptional downregulation. C/EBPb contains three different translation initiation sites that can lead probably by leaky ribosome scanning to the generation of three isoforms of C/EBPb, namely full-length C/EBPb, liver enriched transcriptional activator protein (LAP), and liver enriched inhibitory protein (LIP). When transiently expressed in C33A and HeLa cells, the first two C/EBPb isoforms activate the HPV16 long control region (LCR). LIP, which acts as an antagonist of C/EBPb, 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.