p21WAF1 modulates NF-κB signaling and induces anti-apoptotic protein Bcl-2 in Tax-expressing rat fibroblast

Of the cell cycle-associated genes regulated by human T-cell leukemia virus type-1 (HTLV-1) Tax, cyclin-dependent kinase (CDK) inhibitor p21WAF1 is upregulated in HTLV-1-infected cells. Previously, we reported that p21WAF1 stimulated Tax-dependent NF-κB activation which influences a variety of cellular processes, including proliferation, differentiation, and apoptosis. In HTLV-1-infected cells, Tax is primarily involved in the constitutive activation of NF-κB signaling. Here, we demonstrate that p21WAF1 affects Tax-dependent NF-κB signaling by inducing p100/52, an NF-κB-related protein. W4, a Tax-transformed rat fibroblast cell line, exhibits the constitutive activation of NF-κB signaling, potentially mediated by overexpression of RelB. Ectopic expression of p21WAF1 in W4 cells, which lack endogenous expression due to methylation of the p21WAF1 promoter, induces the expression of p100/52. Bcl-2 expression was also upregulated by ectopic p21WAF1 in this cell line, suggesting that p21WAF1 plays an important role in the regulation of apoptosis by modulating NF-κB signaling in Tax-expressing rat fibroblasts. We also address the expression of NF-κB-related proteins in HTLV-1-infected cells.