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  • Original Article
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HTLV-1 Tax deregulates autophagy by recruiting autophagic molecules into lipid raft microdomains

Abstract

The retroviral oncoprotein Tax from human T-cell leukemia virus type 1 (HTLV-1), an etiological factor that causes adult T-cell leukemia and lymphoma, has a crucial role in initiating T-lymphocyte transformation by inducing oncogenic signaling activation. We here report that Tax is a determining factor for dysregulation of autophagy in HTLV-1-transformed T cells and Tax-immortalized CD4 memory T cells. Tax facilitated autophagic process by activating inhibitor of κB (IκB) kinase (IKK) complex, which subsequently recruited an autophagy molecular complex containing Beclin1 and Bif-1 to the lipid raft microdomains. Tax engaged a crosstalk between IKK complex and autophagic molecule complex by directly interacting with both complexes, promoting assembly of LC3+ autophagosomes. Moreover, expression of lipid raft-targeted Bif-1 or Beclin1 was sufficient to induce formation of LC3+ autophagosomes, suggesting that Tax recruitment of autophagic molecules to lipid rafts is a dominant strategy to deregulate autophagy in the context of HTLV-1 transformation of T cells. Furthermore, depletion of autophagy molecules such as Beclin1 and PI3 kinase class III resulted in impaired growth of HTLV-1-transformed T cells, indicating a critical role of Tax-deregulated autophagy in promoting survival and transformation of virally infected T cells.

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Acknowledgements

We thank Atsushi Koito and Takeo Ohsugi for MT-1 cell line, and Wen Dong, Li Chen, Dan Liu, Di Xiang and Huan Zhang for technical assistance. Research reported in this publication was supported by the National Institute of Allergy And Infectious Diseases of the National Institutes of Health under award number R01AI090113 to H Cheng and was partly supported by the award CA129682 to HG Wang.

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Ren, T., Takahashi, Y., Liu, X. et al. HTLV-1 Tax deregulates autophagy by recruiting autophagic molecules into lipid raft microdomains. Oncogene 34, 334–345 (2015). https://doi.org/10.1038/onc.2013.552

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