The autophagy molecule Beclin 1 maintains persistent activity of NF-κB and Stat3 in HTLV-1-transformed T lymphocytes.

The retroviral oncoprotein Tax from human T cell leukemia virus type 1 (HTLV-1) induces persistent activation of IκB kinase (IKK)/NF-κB signaling, an essential step for initiating HTLV-1 oncogenesis. The regulation of the IKK/NF-κB signaling in HTLV-1-transformed T cells remains incompletely understood. In the present study, we showed that the autophagy molecule Beclin1 not only executed a cytoprotective function through induction of autophagy but also played a pivotal role in maintaining Tax-induced activation of two key survival factors, NF-κB and Stat3. Silencing Beclin1 in HTLV-1-transformed T cells resulted in diminished activities of NF-κB and Stat3 as well as impaired growth. In Beclin1-depleted cells, Tax failed to activate NF-κB and Stat3 at its full capacity. In addition, we showed that Beclin1 interacted with the catalytic subunits of IKK. Further, we observed that selective inhibition of IKK repressed the activities of both NF-κB and Stat3 in the context of HTLV-1-transformation of T cells. Our data, therefore, unveiled a key role of Beclin1 in maintaining persistent activities of both NF-κB and Stat3 in the pathogenesis of HTLV-1-mediated oncogenesis.