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Distinct nuclear body components, PML and SMRT, regulate the trans-acting function of HTLV-1 Tax oncoprotein

Oncogene volume 22, pages 1611–1619 (2003)Cite this article

Abstract

Several viruses target cellular promyelocytic leukemia (PML)-nuclear bodies (PML-NBs) to induce their disruption, marked morphological changes in these structures or the relocation to PML-NB components to the cytoplasm of infected cells. PML conversely interferes with viral replication. We demonstrate that PML acts as a coactivator for the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein without direct binding. Tax was identified within interchromatin granule clusters (IGCs)/RNA splicing bodies (SBs), not PML-NBs; Tax expression did not affect PML-NB formation. Moreover, PML and CBP/p300 cooperatively activated Tax-mediated HTLV-1-LTR-dependent gene expression. Interestingly, two PML mutants, PML-RAR and PMLΔ216-331, which fail to form PML-NBs, could also coactivate Tax-mediated trans-acting function but had no effect on retinoic acid receptor (RAR)- or p53-dependent gene expression. In contrast, SMRT (silencing mediator for retinoic acid and thyroid hormone receptors), a nuclear corepressor found within the matrix-associated deacetylase (MAD) nuclear body, relocalized into Tax-associated nuclear bodies upon coexpression with Tax. SMRT coactivated the trans-acting function of Tax through direct binding. Coexpression of SMRT and PML resulted in an additive activation of Tax trans-acting function. Thus, crosstalk between distinct nuclear bodies may control Tax function.

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Acknowledgements

We thank Dr RM Evans for pCMX PML, pCMX PML-RAR, pSV PMLΔ216-331, and pCMX-mSMRTaFL; Dr M Hatanaka for λHTLV-1, pH2R Tax, PSS serum and the anti-Tax antibody (MI 73); Dr S Yamaoka for pCMV Tax m148 and m319; Dr B Vogelstein for pC53-SN3, Dr T Kiyono for p55Bluc and pCAST2Bluc; Dr K Yokoyama for pCMVp300, Dr I Talianidis for pCMV CBP; and K Watashi for p55cRARE-Luc. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan

    Yasuo Ariumi, Takeshi Ego, Atsushi Kaida, Mikiko Matsumoto & Kunitada Shimotohno

  2. Department of Human Genetics, Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, Graduate School of Medical Sciences, Cornell University, 1275 York Avenue, New York, 10021, NY, USA

    Pier Paolo Pandolfi

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  1. Yasuo Ariumi
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Correspondence to Kunitada Shimotohno.

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Ariumi, Y., Ego, T., Kaida, A. et al. Distinct nuclear body components, PML and SMRT, regulate the trans-acting function of HTLV-1 Tax oncoprotein. Oncogene 22, 1611–1619 (2003). https://doi.org/10.1038/sj.onc.1206244

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