Human T ‐cell leukemia virus type 1 T ax oncoprotein represses the expression of the BCL 11 B tumor suppressor in T ‐cells

Human T‐cell leukemia virus type 1 ( HTLV ‐1) is the etiological agent of adult T cell leukemia ( ATL ), which is an aggressive form of T‐cell malignancy. HTLV ‐1 oncoproteins, Tax and HBZ , play crucial roles in the immortalization of T‐cells and/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that HTLV ‐1‐infected T‐cells have reduced expression of the BCL 11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL 11 B in HTLV ‐1‐infected T‐cells. Lentiviral transduction of Tax in a human T‐cell line repressed the expression of BCL 11 B at both the protein and m RNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF ‐κ B , CREB or PDZ protein pathways still showed a reduced expression of the BCL 11 B protein, thereby implicating a different function of Tax in BCL 11 B downregulation. In addition, the HTLV ‐2 Tax2 protein reduced the BCL 11 B protein expression in T‐cells. Seven HTLV ‐1‐infected T‐cell lines, including three ATL ‐derived cell lines, showed reduced BCL 11 B m RNA and protein expression relative to an uninfected T‐cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing BCL 11 B protein expression in HTLV ‐1‐infected T‐cells; Tax‐mediated repression of BCL 11 B is another mechanism that Tax uses to promote oncogenesis of HTLV ‐1‐infected T‐cells.