title: 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.
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Division of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takachi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Manami
authors.initials: M
authors.lastname: Takahashi-Yoshita
authors.forename: Masaya
authors.initials: M
authors.lastname: Higuchi
authors.forename: Miki
authors.initials: M
authors.lastname: Obata
authors.forename: Yukio
authors.initials: Y
authors.lastname: Mishima
authors.forename: Shujiro
authors.initials: S
authors.lastname: Okuda
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Akihiko
authors.initials: A
authors.lastname: Saitoh
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Green
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000472:pathogenicity*; D015367:Human T-lymphotropic virus 2 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis*; D012191:Retroviridae Proteins; D013601:T-Lymphocytes / Q000821:virology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C479740:BCL11B protein, human; D050976:Basic-Leucine Zipper Transcription Factors; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; C479751:HBZ protein, human T-cell leukemia virus type I; D016328:NF-kappa B; D012097:Repressor Proteins; D012191:Retroviridae Proteins; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; C514970:tax protein, Human T-lymphotrophic virus 1
keywords: Adult T cell leukemia; BCL11B; HBZ; HTLV-1; Tax