Bcl-3 suppresses Tax-induced NF-κB activation through p65 nuclear translocation blockage in HTLV-1-infected cells.

Human T cell leukemia virus type 1 (HTLV-1) Tax-induced persistent activation of the NF-κB pathway is perceived as the primary cause of adult T cell leukemia (ATL), an aggressive leukemia caused by HTLV-1. Although elevated oncoprotein Bcl-3 levels are found in many HTLV-1-infected T cell lines and ATL cells, the role of Bcl-3 in the malignant progression caused by HTLV-1 retrovirus remains poorly understood. We confirmed, in the present study, that the Tax-induced NF-κB activation involves the regulation of Bcl-3. Both knockdown and overexpression of Bcl-3 inhibit the Tax-induced NF-κB activation. Similarly, excessive Bcl-3 inhibits the NF-κB/DNA binding activity and significantly decreases Tax-induced p65 nuclear translocation. The present results demonstrate the pleiotropic roles of Bcl-3 in Tax-induced NF-κB activation and indicate that a balance in the aberrant Bcl-3 expression may be established to play an important role in the maintenance of proliferation and inhibition of apoptosis in HTLV-1-infected and ATL cells.