Tax protein-induced expression of antiapoptotic Bfl-1 protein contributes to survival of human T-cell leukemia virus type 1 (HTLV-1)-infected T-cells.

The Journal of Biological Chemistry
Héloïse MacaireHélène Valentin

Abstract

Human T lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL). ATLL is a severe malignancy with no effective treatment. HTLV-1 regulatory proteins Tax and HTLV-1 basic leucine zipper factor (HBZ) play a major role in ATLL development, by interfering with cellular functions such as CD4(+) T-cell survival. In this study, we observed that the expression of Bfl-1, an antiapoptotic protein of the Bcl-2 family, is restricted to HTLV-1-infected T-cell lines and to T-cells expressing both Tax and HBZ proteins. We showed that Tax-induced bfl-1 transcription through the canonical NF-κB pathway. Moreover, we demonstrated that Tax cooperated with c-Jun or JunD, but not JunB, transcription factors of the AP-1 family to stimulate bfl-1 gene activation. By contrast, HBZ inhibited c-Jun-induced bfl-1 gene activation, whereas it increased JunD-induced bfl-1 gene activation. We identified one NF-κB, targeted by RelA, c-Rel, RelB, p105/p50, and p100/p52, and two AP-1, targeted by both c-Jun and JunD, binding sites in the bfl-1 promoter of T-cells expressing both Tax and HBZ. Analyzing the potential role of antiapoptotic Bcl-2 proteins in HTLV-1-infected T-cell survival, we demonstrated that these cells...Continue Reading

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Citations

Feb 27, 2013·PloS One·Selma Olsson ÅkefeldtChristine Delprat
Jul 15, 2015·Journal of Oncology·Christophe Nicot
Dec 8, 2016·Biopharmaceutics & Drug Disposition·Bernadette EspanaCaroline Prouillac
Nov 27, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mohammad KarimiBehzad Baradaran
May 4, 2018·The FEBS Journal·Edward William Harhaj, Chou-Zen Giam
Jun 19, 2014·The Journal of Biological Chemistry·Elizabeth JaworskiFatah Kashanchi
Aug 25, 2012·Blood·Camille Abboud
Feb 8, 2018·Annual Review of Pathology·Marco PizziGiorgio Inghirami
May 4, 2017·Immunological Reviews·Kun-Po LiDavid A Hildeman
Apr 13, 2018·Frontiers in Microbiology·Sara MoodadHiba El Hajj
Dec 15, 2019·Pathogens·Stefania FochiMaria Grazia Romanelli
Jul 11, 2020·Pathogens·Suchitra Mohanty, Edward W Harhaj
Sep 12, 2020·Retrovirology·Sebastian MillenAndrea K Thoma-Kress

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