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HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L)

Oncogene volume 24, pages 1262–1271 (2005)Cite this article

Abstract

Crk-associated substrate lymphocyte type (Cas-L) is a docking protein that is heavily tyrosine phosphorylated by the engagement of β1 integrins in T cells. In the present study, we attempted to evaluate the role of Cas-L in the pathophysiology of adult T-cell leukemia (ATL). Examination of peripheral blood mononuclear cells from ATL patients as well as ATL-derived T cell lines showed an elevation of Cas-L in these cells. We showed that tyrosine phosphorylation as well as expression of Cas-L was markedly elevated through the induction of human T-lymphotropic virus type I (HTLV-I) Tax in JPX-9 cells, with these cells showing marked motile behavior on the ligands for integrins. We next performed yeast two-hybrid screening of cDNA library from an HTLV-I-transformed T cell line, which resulted in the identification of Tax as a putative binding partner for Cas-L. Co-precipitation experiments revealed that the serine-rich region of Cas-L might serve as the binding site with the highest affinity for Tax. Co-localization study showed that Tax and Cas-L partly merged in the cytoplasm. Finally, we showed that exogenous Cas-L inhibited Tax-mediated transactivation of nuclear factor κB (NF-κB), while Tax-independent activation of NF-κB remained intact, hence indicating that Cas-L might specifically regulate Tax-NF-κB pathway.

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Acknowledgements

We appreciate Yoshiyuki Ohashi, Rikako Miyake-Nishijima, Seiji Kobayashi, Kei Ohnuma, Masahiko Uchiyama, Rika Ouchida, and Noriaki Shimizu for help in some experiments. We greatly acknowledge Shoji Yamaoka for critical reading of the manuscript and invaluable discussion. This work was supported by grants-in-aid from the Ministry of Education, Science, and Culture and Ministry of Health, Labor and Welfare, of Japan.

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Authors and Affiliations

  1. Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Satoshi Iwata, Akiko Souta-Kuribara, Takahiro Sasaki, Osamu Hosono, Hiroshi Kawasaki, Hirotoshi Tanaka & Chikao Morimoto

  2. Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA, 02115, USA

    Akio Yamakawa

  3. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo, 160-8582, Japan

    Takatsune Shimizu

  4. Department of Lymphoma/Myeloma UT, MD Anderson Cancer Center, Houston, TX, 77030, USA

    Nam H Dang

  5. Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Toshiki Watanabe

  6. Division of Host Response, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Naomichi Arima

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  1. Satoshi Iwata
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Correspondence to Chikao Morimoto.

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Iwata, S., Souta-Kuribara, A., Yamakawa, A. et al. HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L). Oncogene 24, 1262–1271 (2005). https://doi.org/10.1038/sj.onc.1208261

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