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Nuclear localization of Tob is important for regulation of its antiproliferative activity

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Abstract

tob is a member of an antiproliferative gene family that includes btg1, pc3/tis21/btg2, pc3b, ana/btg3, and tob2. Exogenous overexpression of the family proteins suppresses cell proliferation. These proteins participate in transcriptional regulation of several genes. Here, we show that Tob is a nuclear protein that is imported into the nucleus through a nuclear localization signal (NLS)-mediated mechanism. Mutation in the NLS sequence of Tob affects its nuclear localization and impairs antiproliferative activity. Additionally, Tob contains a nuclear export signal (NES). In oncogenic ErbB2-transformed cells, nuclear export of Tob is facilitated by NES-mediated mechanism, resulting in decrease of its antiproliferative activity. These results indicate that regulation of nuclear localization of Tob is important for its antiproliferative activity.

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Acknowledgements

We thank J Inoue, Y Yamanashi, N Ikematsu, R Ajima, N Nakamura, M Watanabe, T Miyasaka and L Amy for valuable discussions. We thank Dr T Seito at IBL for his kind supply of the monoclonal anti-Tob antibody, and Dr M Yoshida for generously supplying leptomycin B. We also thank Dr JC Luo for kind gift of pEGFP–β-Gal vector and thank Dr BR Henderson for pRev(1.4)–GFP vector.

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  1. Division of Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan

    Junko Kawamura-Tsuzuku, Toru Suzuki, Yutaka Yoshida & Tadashi Yamamoto

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  1. Junko Kawamura-Tsuzuku
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  2. Toru Suzuki
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  3. Yutaka Yoshida
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  4. Tadashi Yamamoto
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Correspondence to Tadashi Yamamoto.

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Kawamura-Tsuzuku, J., Suzuki, T., Yoshida, Y. et al. Nuclear localization of Tob is important for regulation of its antiproliferative activity. Oncogene 23, 6630–6638 (2004). https://doi.org/10.1038/sj.onc.1207890

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  • DOI: https://doi.org/10.1038/sj.onc.1207890

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