@prefix dcat: . @prefix dct: . @prefix foaf: . @prefix vcard: . @prefix xsd: . a dcat:Dataset ; dct:description """ Human T lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL) that develops after several decades and for which there is no effective treatment. Among the viral proteins of HTLV-1, Tax and HBZ play a major role in the development of ATLL. If Tax participates in the initiation of leukemogenesis from the early stages, HBZ rather plays a role in maintaining the tumor phenotype in the late stages. The aims of our study were to better understand the regulation of Bfl-1 and Bcl-xL anti-apoptotic protein expression by Tax and HBZ viral proteins, as well as their role in the survival of HTLV-1-infected T-cells to propose new therapeutic strategies. We showed that Tax induces Bfl-1 and Bcl-xL expression via the NF-κB pathway, whereas HBZ has no effect on their expression. Tax also cooperates with c-Jun and JunD transcription factors of AP-1 family to increase the expression of these anti-apoptotic genes. By contrast, HBZ modulates the Tax-induced bfl-1 trans-activation. Altogether, our data indicate that Tax plays a key role in activating Bfl-1 and Bcl-xL expression and suggests that Bfl-1 and Bcl-xL are potentially expressed during the early and the late stages of ATLL development. Using short hairpin RNA strategy, we then showed that Bfl-1 and/or Bcl-xL are involved in HTLV-1-infected T-cell line survival, indicating that Bfl-1 and Bcl-xL represent potential therapeutic targets in the case of ATLL. One approach currently being developed in anti-cancer drug discovery is to search for small inhibitory compounds targeting anti-apoptotic proteins of the Bcl-2 family. But so far, no drug specifically targeting Bfl-1 is available. In collaboration with the IMAXIO Company, we have identified 83 molecules able to inhibit Bfl-1 anti-apoptotic activity using two high-throughput screening. One of these molecules specifically induced the death of HTLV-1-infected T-cell for which Bfl-1 represents a survival gene. This work provides new insight for long-term development of future drugs directed against Bfl-1 and should allow us to propose new therapeutic strategy for ATLL treatment """ ; dct:identifier "NNT: 2011LYO10357" ; dct:issued "2026-05-09T18:23:44.471994"^^xsd:dateTime ; dct:language "fr" ; dct:modified "2026-05-09T18:23:44.471999"^^xsd:dateTime ; dct:publisher ; dct:title "Regulation of Bfl-1 and Bcl-xL anti-apoptotic protein expression by the HTLV-1 Tax and HBZ proteins and identification of small therapeutic molecules directed against Bfl-1 v" ; dcat:contactPoint [ a vcard:Organization ; vcard:fn "CCSD" ] ; dcat:distribution ; dcat:keyword "adult-t-cell-leukemia--lymphoma-atll", "apoptose", "apoptosis", "bcl-xl", "bfl-1", "cible-therapeutique", "hbz", "human-t-cell-leukemia-virus-type-1", "infoeu-reposemanticsdoctoralthesis", "leucemie--lymphome-t-de-ladulte-atll", "sdvsalife-sciences-q-bioagricultural-sciences", "tax", "therapeutic-target", "theses", "virus-humain-t-lymphotrope-de-type-1-htlv-1" ; dcat:landingPage . a dcat:Distribution ; dct:format "HTML" ; dct:issued "2026-05-09T18:23:44.475322"^^xsd:dateTime ; dct:modified "2026-05-09T18:23:44.456770"^^xsd:dateTime ; dct:title "Regulation of Bfl-1 and Bcl-xL anti-apoptotic protein expression by the HTLV-1 Tax and HBZ proteins and identification of small therapeutic molecules directed against Bfl-1 v" ; dcat:accessURL . a foaf:Agent ; foaf:name "test_moissonnage_selune" . a foaf:Document .