Identification of CD44 as a downstream target of noncanonical NF-κB pathway activated by Human T-cell leukemia virus type 1-encoded Tax protein

Jing Zhang, Osamu Yamada, Shinya Kida, Yoshihisa Matsushita, Shoji Yamaoka, Haorile Chagan-Yasutan, Toshio Hattori

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Our previous study showed Human T-cell leukemia virus type 1 Tax induces osteopontin (OPN) expression by transactivating its promoter. As an extension, we investigated here the possible influence of Tax on CD44, an important receptor for OPN. Co-expression of Tax, but not its NF-κB-defective mutant, significantly increased the reporter gene expression directed by CD44 promoter. Tax-mediated CD44 activation was largely diminished by disrupting an element similar to the noncanonical κβ site found in other IKKα target genes, and further, co-transfection of RelB siRNA abolished CD44 induction by Tax, suggesting an involvement of noncanonical NF-κB pathway in Tax-mediated transactivation. Consistently, chromatin immunoprecipitation revealed a specific interaction of CD44 promoter with RelB-containing complex. Together, these results indicate that D44 gene is one of the downstream target genes of aberrantly activated noncanonical NF-κB signaling by Tax, providing an additional line of evidence explaining how Tax-induced NF-κB signaling is integrated into a fate-determining cellular program.

Original languageEnglish
Pages (from-to)244-252
Number of pages9
JournalVirology
Volume413
Issue number2
DOIs
Publication statusPublished - 2011 May 10

Keywords

  • CD44
  • HTLV-1
  • Noncanonical NF-B signaling
  • RelB
  • Tax

ASJC Scopus subject areas

  • Virology

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