title: Human T-cell leukemia virus type 1 Tax protein interacts with and mislocalizes the PDZ domain protein MAGI-1.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). HTLV-1 encodes the oncoprotein Tax1, which is essential for immortalization of human T-cells and persistent HTLV-1 infection in vivo. Tax1 has a PDZ binding motif (PBM) at its C-terminus. This motif is crucial for the transforming activity of Tax1 to a T-cell line and persistent HTLV-1 infection. Tax1 through the PBM interacts with PDZ domain proteins such as Dlg1 and Scribble, but it has not been determined yet, which cellular PDZ proteins mediate the functions of Tax1 PBM. Here we demonstrate that Tax1 interacts with the PDZ domain protein MAGI-1 in a PBM-dependent manner, and the interaction mislocalizes MAGI-1 from the detergent-soluble to the detergent-insoluble cellular fraction in 293T cells and in HTLV-1-infected T-cells. In addition, Tax1-transformation of a T-cell line from interleukin (IL)-2-dependent to IL-2-independent growth selects cells with irreversibly reduced expression of MAGI-1 at mRNA level. These findings imply that Tax1, like other viral oncoproteins, targets MAGI-1 as a mechanism to suppress its anti-tumor functions in HTLV-1-infected cells to contribute to the transforming activity of T-cells and persistent HTLV-1 infection.
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Grace Naswa
authors.initials: GN
authors.lastname: Makokha
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Masaya
authors.initials: M
authors.lastname: Higuchi
authors.forename: Suguru
authors.initials: S
authors.lastname: Saito
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002472:Cell Transformation, Viral; D015536:Down-Regulation; D016356:Gene Products, tax / Q000378:metabolism*; D051528:Guanylate Kinases; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D054731:PDZ Domains; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D016356:Gene Products, tax; D051528:Guanylate Kinases; C113338:MAGI1 protein, human