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Human T-cell leukemia virus type 1 Tax induces an aberrant clustering of the tumor suppressor Scribble through the PDZ domain-binding motif dependent and independent interaction

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Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia. HTLV-1 Tax1 transforming protein interacts with several PDZ domain-containing proteins, and the interaction is associated with the transforming activities of Tax1 as well as persistent HTLV-1 infection. In this study, we show that Tax1 interacts with the tumor suppressor Scribble containing PDZ domains. Unlike other Tax1-interacting PDZ domain proteins, the PDZ domain-binding motif (PBM) of Tax1 was not required for the interaction with transiently expressed Scribble in 293T cells, but it was essential for the interaction with endogenous Scribble. Endogenous Scribble in 293T cells was primarily localized at the plasma membrane and colocalized with Tax1 but not Tax1∆C lacking PBM, whereas transiently expressed Scribble was localized in the cytoplasm and colocalized with Tax1∆C as well as Tax1, thus suggesting that Tax1 is recruited to the site of endogenous Scribble, such as the plasma membrane, in a PBM-dependent manner, and thereafter it interacts with Scribble in a PBM-independent and PBM-dependent manner. Endogenous Scribble was diffusely localized at the plasma membrane of HTLV-1-uninfected T-cell lines, whereas it colocalized with Tax1 as small and large aggregate at the plasma membranes. These results suggest that Tax1 through two binding sites induce aberrant clustering of Scribble, thereby altering the functions in HTLV-1-infected cells, which may thus play a role in persistent HTLV-1 infection and the pathogenesis.

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Acknowledgments

We thank Dr. William W. Hall, Dr. Tetsu Akiyama, and Dr. Renaud Mahieux for providing the Tax2B plasmid, the Dlg1 plasmid, and the antibody against Tax2B, respectively. We also thank the Takeda Pharmaceutical Company for providing recombinant human IL-2. We also thank Misako Tobimatsu for her excellent technical assistance. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas and for Scientific Research (C) of Japan.

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Authors and Affiliations

  1. Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan

    Masaaki Okajima, Masahiko Takahashi, Masaya Higuchi, Toshiaki Ohsawa, Sakiko Yoshida, Masayasu Oie & Masahiro Fujii

  2. Division of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan

    Masaaki Okajima & Fumitake Gejyo

  3. Department of Structural Pathology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan

    Yutaka Yoshida

  4. Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Uehara 207, Nishihara-cho, Nakagami-gun, Okinawa, 903-0215, Japan

    Yuetsu Tanaka

Authors
  1. Masaaki Okajima
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  2. Masahiko Takahashi
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  3. Masaya Higuchi
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  4. Toshiaki Ohsawa
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  7. Masayasu Oie
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  8. Yuetsu Tanaka
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  9. Fumitake Gejyo
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  10. Masahiro Fujii
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Correspondence to Masahiro Fujii.

Additional information

M. Okajima and M. Takahashi contributed equally to this study.

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Okajima, M., Takahashi, M., Higuchi, M. et al. Human T-cell leukemia virus type 1 Tax induces an aberrant clustering of the tumor suppressor Scribble through the PDZ domain-binding motif dependent and independent interaction. Virus Genes 37, 231–240 (2008). https://doi.org/10.1007/s11262-008-0259-4

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