Human T‐cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T‐cells

Abstract

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 BCL11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral transduction of Tax in a human T-cell line repressed the expression of BCL11B at both the protein and mRNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF-κB, CREB or PDZ protein pathways still showed a reduced expression of the BCL11B protein, thereby implicating a different function of Tax in BCL11B downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL-derived cell lines, showed reduced BCL11B mRNA 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 BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of HTLV-1-infected T-cells.

Murine leukemia virus (MLV) P50 protein induces cell transformation via transcriptional regulatory function

“…6 A). Like the regulatory proteins Tat of HIV and Tax of HTLV [ 65 , 66 ], which transactivate viral transcription (for review, [ 67 , 68 ]), P50 also acted as a regulatory protein. Indeed, P50 transrepressed the viral transcription and consequently decreased the FL RNA translation (Fig.…”

Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts

“…BCL11B is implicated in multiple biological processes, including cell proliferation ( 51 ), apoptosis ( 52 ) and the immune response ( 53 ), as well as different pathological conditions, including cancer ( 54 ), inflammation ( 55 ), cardiac hypertrophy ( 56 ) and human immunodeficiency virus latency ( 57 ). Previous studies have demonstrated that BCL11B also contributes to T-cell development and T-cell identity ( 53 , 58 , 59 ). Additionally, BCL11B serves a critical role in the production and release of cytokines, including IFN-γ, IL-5 and IL-13 ( 60 – 62 ).…”

Aneuploidy and oncoviruses

“…Almost 5% of HTLV‐1‐positive individuals develop adult T cell leukemia/lymphoma (ATL), though the process of disease occurrence remains poorly understood . The virus encodes two proteins that have been reported to result in oncogenesis: Tax and HTLV‐1 basic leucine zipper factor (HBZ) …”