Human T-cell leukemia virus type 1 Tax modulates interferon-α signal transduction through competitive usage of the coactivator CBP/p300

Jing Zhang, Osamu Yamada, Kenji Kawagishi, Hiromasa Araki, Shoji Yamaoka, Toshio Hattori, Kunitada Shimotohno

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

We describe here Tax protein of human T-cell leukemia virus type 1 (HTLV-1) as an interferon (IFN)-α antagonist counteracting the transactivation function of IFN-stimulated gene factor 3 (ISGF3). Co-expression of Tax, but not the Tax mutant unable to bind to CBP, significantly inhibited the reporter gene expression directed by IFN-stimulated regulatory elements, despite that the formation of DNA-binding ISGF3 complex was unaffected. Gene activation induced by STAT2 transcription domain was also inhibited by expression of Tax. Furthermore, Tax-mediated transcriptional inhibition was reversed by overexpression of p300. These observations indicate that Tax interferes with IFN-α-induced JAK-STAT pathway by competition with STAT2 for CBP/p300 binding. Consistently, GST pull-down assay showed that Tax dose-dependently inhibited binding of STAT2 to p300. This study suggests that Tax may prevent IFN-α from exerting its antiviral, antiproliferative and proapoptotic effects, thereby contributing to persistent viral infection and HTLV-1-associated oncogenesis.

Original languageEnglish
Pages (from-to)306-313
Number of pages8
JournalVirology
Volume379
Issue number2
DOIs
Publication statusPublished - 2008 Sep 30

Keywords

  • CBP/p300 coactivator
  • HTLV-1
  • IFN-α signaling
  • Tax

ASJC Scopus subject areas

  • Virology

Fingerprint Dive into the research topics of 'Human T-cell leukemia virus type 1 Tax modulates interferon-α signal transduction through competitive usage of the coactivator CBP/p300'. Together they form a unique fingerprint.

Cite this