Human T-cell leukemia virus type 1 Tax protein interacts with and mislocalizes the PDZ domain protein MAGI-1
Grace Naswa Makokha
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Search for more papers by this authorMasahiko Takahashi
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Search for more papers by this authorMasaya Higuchi
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Search for more papers by this authorSuguru Saito
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Search for more papers by this authorYuetsu Tanaka
Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan
Search for more papers by this authorCorresponding Author
Masahiro Fujii
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
To whom correspondence should be addressed.
E-mail: [email protected]
Search for more papers by this authorGrace Naswa Makokha
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Search for more papers by this authorMasahiko Takahashi
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Search for more papers by this authorMasaya Higuchi
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Search for more papers by this authorSuguru Saito
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Search for more papers by this authorYuetsu Tanaka
Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan
Search for more papers by this authorCorresponding Author
Masahiro Fujii
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
To whom correspondence should be addressed.
E-mail: [email protected]
Search for more papers by this authorAbstract
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.
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