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 (HTI.V-1) Tax, cyclin-dependent kinase (CDK) inhibitor p21(WAF1) is upregulated in HTLV-1-infected cells. Previously, we reported that p21(WAF1) stimulated Tax-dependent NF-kappaB 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-kappaB signaling. Here, we demonstrate that p21(WAF1) affects Tax-dependent NF-kappaB signaling by inducing p 100/52, an NF-kappaB-related protein. W4, a Tax-transformed rat fibroblast cell line, exhibits the constitutive activation of NF-kappaB signaling, potentially mediated by overexpression of RelB. Ectopic expression of p21(WAF1) in W4 cells, which lack endogenous expression due to methylation of the p21(WAFI) promoter, induces the expression of p 100/52. Bcl-2 expression was also upregulated by ectopic p21(WAF1) in this cell line, suggesting that p21(WAFI) plays an important role in the regulation of apoptosis by modulating NF-kappaB signaling in Tax-expressing rat fibroblasts. We also address the expression of NF-kappaB-related proteins in HTLV-1 -infected cells. (C) 2004 Elsevier Inc. All rights reserved.