New insight into the oncogenic mechanism of the retroviral oncoprotein Tax

Abstract

Human T cell leukemia virus type 1 (HTLV-1), an etiological factor that causes adult T cell leukemia and lymphoma (ATL), infects over 20 million people worldwide. About 1 million of HTLV-1-infected patients develop ATL, a highly aggressive non-Hodgkin's lymphoma without an effective therapy. The pX region of the HTLV-1 viral genome encodes an oncogenic protein, Tax, which plays a central role in transforming CD4+ T lymphocytes by deregulating oncogenic signaling pathways and promoting cell cycle progression. Expression of Tax following viral entry is critical for promoting survival and proliferation of human T cells and is required for initiation of oncogenesis. Tax exhibits diverse functions in host cells, and this oncoprotein primarily targets IκB kinase complex in the cytoplasm, resulting in persistent activation of NF-κB and upregulation of its responsive gene expressions that are crucial for T cell survival and cell cycle progression. We here review recent advances for the pathological roles of Tax in modulating IκB kinase activity. We also discuss our recent observation that Tax connects the IκB kinase complex to autophagy pathways. Understanding Tax-mediated pathogenesis will provide insights into development of new therapeutics in controlling HTLV-1- associated diseases.

Keywords

human T cell leukemia virus type 1 / IκB kinase complex / NF-κB / lipid raft microdomains / autophagy / Beclin1-PI3KC3-Bif1 complex

References

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