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  • Oral presentation
  • Open Access

Tax as a therapeutic target in ATL

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Retrovirology201512 (Suppl 1) :O20

  • Published:


  • Clinical Response
  • Clinical Activity
  • Transformed Cell
  • Partner Protein
  • Nuclear Body

The HTLV-1 Tax transactivator initiates transformation in adult T-cell leukemia/lymphoma (ATL), a highly aggressive chemotherapy-resistant malignancy. The arsenic/interferon combination, which triggers degradation of the Tax on coprotein, selectively induces apoptosis of ATL cell lines and has significant clinical activity in Tax-driven murine ATL or patients. Yet, the role of Tax expression in maintaining the transformed phenotype and of Tax loss in ATL response is disputed and the molecular mechanisms driving degradation remain elusive. Here we demonstrate that ATL-derived or HTLV-1 transformed cells are addicted to continuous Tax expression, suggesting that Tax degradation underlies clinical responses to the arsenic/interferon combination. The latter enforces PML nuclear body (NB) formation and partner protein recruitment. In arsenic/interferon-treated ATL-derived cells, Tax is recruited onto NBs, undergoes PML-dependent hyper-sumoylation by SUMO2/3, but not SUMO1, ubiquitination by RNF4 and proteasome-dependent degradation. Thus, the arsenic/interferon combination clears ATL through degradation of its Tax driver and could have broader therapeutic value by promoting degradation of other pathogenic sumoylated proteins.

Authors’ Affiliations

Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
Université Paris Diderot, Sorbonne Paris Cité, Hôpital St. Louis 1, Avenue Claude Vellefaux, 75475 PARIS cedex 10, France
INSERM UMR 944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St. Louis 1, Avenue Claude Vellefaux, 75475 PARIS cedex 10, France
CNRS UMR 7212, Hôpital St. Louis 1, Avenue Claude Vellefaux, 75475 PARIS cedex 10, France
AP-HP, Service de Biochimie, Hôpital St. Louis 1, Avenue Claude Vellefaux 75475 PARIS cedex 10, France
College de France, Place Marcelin Berthelot, 75005 PARIS, France
CNRS UMR 8147, Hôpital Necker, PARIS cedex 15, France


© Dassouki et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.