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

Biochemical and Biophysical Research Communications
Li ChenHua Cheng

Abstract

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.

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Citations

Apr 11, 2017·Acta Pharmacologica Sinica·Lan-Lan ZhangJi-Long Chen
May 4, 2018·The FEBS Journal·Edward William Harhaj, Chou-Zen Giam
Dec 15, 2019·Pathogens·Stefania FochiMaria Grazia Romanelli
Apr 2, 2020·Cell Death & Disease·Daniela VerzellaFrancesca Zazzeroni
Mar 18, 2020·Frontiers in Cell and Developmental Biology·Tiziana VescovoManuela Antonioli
Nov 9, 2018·Frontiers in Cellular and Infection Microbiology·Michelle L PleetFatah Kashanchi
Mar 9, 2018·Frontiers in Microbiology·Stefania FochiMaria G Romanelli
Jul 11, 2020·Pathogens·Suchitra Mohanty, Edward W Harhaj
Mar 26, 2021·Frontiers in Oncology·Alejandra SuaresOmar Coso
Apr 20, 2021·Frontiers in Oncology·Nicolás DucasaMaria Noé Garcia
Jul 13, 2021·World Journal of Stem Cells·Harpreet K MandhairRamin Radpour
Sep 17, 2021·Biochemical Pharmacology·Jeong-Su ParkYoon-Seok Roh

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