I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

Shuichi Kusano, Makoto Yoshimitsu, Miho Hachiman, Masanori Ikeda

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability.

Original languageEnglish
Pages (from-to)219-227
Number of pages9
JournalVirology
Volume486
DOIs
Publication statusPublished - Dec 1 2015

Keywords

  • HTLV-1
  • I-mfa-domain protein
  • LTR
  • NF-κB
  • Protein-protein interaction
  • Tax
  • Transcription

ASJC Scopus subject areas

  • Virology

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