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

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-kappa B-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 kappa beta site found in other IKK alpha target genes, and further, co-transfection of RelB siRNA abolished CD44 induction by Tax, suggesting an involvement of noncanonical NF-kappa B pathway in Tax-mediated transactivation. Consistently, chromatin immunoprecipitation revealed a specific interaction of CD44 promoter with ReIB-containing complex. Together, these results indicate that D44 gene is one of the downstream target genes of aberrantly activated noncanonical NF-kappa B signaling by Tax, providing an additional line of evidence explaining how Tax-induced NF-kappa B signaling is integrated into a fate-determining cellular program. (C) 2011 Elsevier Inc. All rights reserved.