Inhibition of human papillomavirus-16 long control region activity by interferon-gamma overcome by p300 overexpression

✍ Scribed by Véronique Fontaine; Els van der Meijden; Jan ter Schegget

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 236 KB
• Volume: 31
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.1036

✦ Synopsis

Abstract

Although interferons (IFNs) are currently used in the treatment of various human papillomavirus (HPV)‐associated lesions, their mechanisms of action are still unclear. In this study, we clearly demonstrated that IFN‐γ was a strong inhibitor of HPV‐16 long control region (LCR) activity in two human cervical carcinoma cell lines. The effect of IFN‐γ was dose dependent. We investigated whether the effect of IFN‐γ on HPV‐16 LCR could involve the inhibition of the CREB‐binding protein (CBP)/p300 family of transcriptional coactivators. In support of this model, we demonstrated by transfection experiments that a 12S E1A mutant (RG2), which interacts poorly with p300 and CBP in comparison to wild‐type E1A, was less able to repress human papillomavirus (HPV) 16 long control region (LCR) than wild‐type E1A. More important, overexpression of p300 was able to increase the HPV‐16 LCR activity and to overcome inhibition by IFN‐γ. Finally, we demonstrated that p300 could cooperate with c‐jun to activate HPV‐16 LCR. According to our results, IFN‐γ might inhibit HPV‐16 LCR transcription by activating the signal transducer and activator of transcription 1α, which in turn might compete for p300/CBP binding with specific transcription factors involved in LCR activation. © 2001 Wiley‐Liss, Inc.