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The retroviral oncoprotein Tax targets the coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication

Nature Cell Biology volume 8, pages 717–724 (2006)Cite this article

Abstract

Emerging evidence suggests that supernumerary centrosomes drive genome instability and oncogenesis1,2,3. Human T-cell leukaemia virus type I (HTLV-I) is etiologically associated with adult T-cell leukaemia (ATL)4. ATL cells are aneuploid, but the causes of aneuploidy are incompletely understood5,6. Here, we show that centrosome amplification is frequent in HTLV-I-transformed cells and that this phenotype is caused by the viral Tax oncoprotein. We also show that the fraction of Tax protein that localizes to centrosomes interacts with TAX1BP2, a novel centrosomal protein composed almost entirely of coiled-coil domains. Overexpression of TAX1BP2 inhibited centrosome duplication, whereas depletion of TAX1BP2 by RNAi resulted in centrosome hyperamplification. Our findings suggest that the HTLV-I Tax oncoprotein targets TAX1BP2 causing genomic instability and aneuploidy.

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Figure 1: Centrosome amplification in HTLV-I-transformed and Tax-expressing cells.
Figure 2: Interaction between Tax and TAX1BP2.
Figure 3: TAX1BP2 is a centrosomal protein.
Figure 4: TAX1BP2 inhibits centrosome duplication.
Figure 5: Tax induces centrosome overduplication through targeting TAX1BP2.

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Acknowledgements

We thank K.-T. Chin, A.C.S. Chun and Y.T. Siu for critical reading of the manuscript. This work was supported by a grant to D.-Y.J. (HKU 7249/01M) from the Hong Kong Research Grants Council. D.-Y.J. is a Leukemia and Lymphoma Society Scholar and a recipient of a National Institutes of Health GRIP New Foreign Investigator Award (R01 TW06186-01) and National Natural Science Foundation of China Young Investigator Award (30029001). Work in the laboratory of K.-T.J. was supported through intramural funds from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong

    Yick-Pang Ching, Shing-Fai Chan & Dong-Yan Jin

  2. Department of Pathology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong

    Yick-Pang Ching

  3. Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, 9000 Rockville Pike, Bethesda, 20892–0460, MD, USA

    Kuan-Teh Jeang

  4. Center for Neuroscience and Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA

    Shing-Fai Chan

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Contributions

D.-Y.J. and K.-T.J. wrote the manuscript. Y.-P.C. and D.-Y.J., assisted by S.-F.C., designed, performed and analysed all experiments. K.-T.J. provided reagents and guidance in project planning. D.-Y.J. was responsible for the conceptualization and execution of the study.

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Correspondence to Dong-Yan Jin.

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Supplementary Figures S1, S2, S3, S4 and S5 (PDF 1055 kb)

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Ching, YP., Chan, SF., Jeang, KT. et al. The retroviral oncoprotein Tax targets the coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication. Nat Cell Biol 8, 717–724 (2006). https://doi.org/10.1038/ncb1432

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