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Ubiquitination-dependent, proteasomal degradation of the retroviral oncoprotein Tax by niclosamide, an anti-helminthic molecule

Retrovirology201411 (Suppl 1) :P148

https://doi.org/10.1186/1742-4690-11-S1-P148

  • Published:

Keywords

  • Viral Gene
  • Proteasomal Degradation
  • Aggressive Form
  • Subsequent Degradation
  • Oncogenic Signaling

Adult T cell leukemia and lymphoma (ATL) is a highly aggressive form of hematological malignancies, which is caused by chronic infection of human T cell leukemia virus type 1 (HTLV-1). The viral genome encodes an oncogenic protein Tax that plays a key role in trans activating viral gene transcription and in deregulating cellular oncogenic signaling to promote survival and proliferation of virally infected T cells. Hence, Tax is a desirable therapeutic target, particularly at early stage of HTLV-1-mediated oncogenesis. We here show that niclosamide, an anti-helminthic molecule, induced apoptosis of HTLV-1-transformed T cells. Niclosamide promoted formation of polyubiquitinated Tax protein aggregate, facilitating its subsequent degradation in proteasome. Consistent with niclosamide-mediated Tax degradation, the transcription of HTLV-1 viral genes is suppressed. Furthermore, niclosamide inhibited the activities of MAPK/ERK and Stat3, and down regulated pro-survival Bcl-2 family members such as Mcl-1. Since Tax, Stat3 and Mcl-1 are growth-promoting molecules in HTLV-1-transformed T cells, our data demonstrated a novel mechanism of niclosamide in inducing polyubiquitination-dependent degradation of Tax and certain cellular pro-survival molecules, thereby promoting apoptosis of HTLV-1-associated leukemia.

Authors’ Affiliations

(1)
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
(2)
Penn State Hershey Cancer Institute, Hershey, PA, USA

Copyright

© Xiang et al; licensee BioMed Central Ltd. 2014

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 (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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