Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Virology. 2013 Sep 1;443(2):226-35. doi: 10.1016/j.virol.2013.04.032. Epub 2013 Jun 18.
Human T-cell leukemia virus type 1 (HTLV-1) Tax (Tax1) plays crucial roles in leukemogenesis in part through activation of NF-κB. In this study, we demonstrated that Tax1 activated an NF-κB binding (gpκB) site of the gp34/OX40 ligand gene in a cell type-dependent manner. Our examination showed that the gpκΒ site and authentic NF-κB (IgκB) site were activated by Tax1 in hematopoietic cell lines. Non-hematopoietic cell lines including hepatoma and fibroblast cell lines were not permissive to Tax1-mediated activation of the gpκB site, while the IgκB site was activated in those cells in association with binding of RelB. However RelA binding was not observed in the gpκB and IgκB sites. Our results suggest that HTLV-1 Tax1 fails to activate the canonical pathway of NF-κB in non-hematopoietic cell lines. Cell type-dependent activation of NF-κB by Tax1 could be associated with pathogenesis by HTLV-1 infection.
人类 T 细胞白血病病毒 1 型(HTLV-1)Tax(Tax1)通过激活 NF-κB 在白血病发生中起关键作用。在这项研究中,我们证明 Tax1 以细胞类型依赖性方式激活了 gp34/OX40 配体基因的 NF-κB 结合(gpκB)位点。我们的检查表明,gpκΒ 位点和真实的 NF-κB(IgκB)位点在造血细胞系中被 Tax1 激活。非造血细胞系,包括肝癌和成纤维细胞系,不允许 Tax1 介导的 gpκB 位点的激活,而 IgκB 位点在与 RelB 结合的同时在这些细胞中被激活。然而,在 gpκB 和 IgκB 位点没有观察到 RelA 结合。我们的结果表明,HTLV-1 Tax1 不能在非造血细胞系中激活 NF-κB 的经典途径。Tax1 对 NF-κB 的细胞类型依赖性激活可能与 HTLV-1 感染的发病机制有关。