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The transcription factor SP3 drives TNF-α expression in response to Smac mimetics.
Beug, Shawn T; Cheung, Herman H; Sanda, Tarun; St-Jean, Martine; Beauregard, Caroline E; Mamady, Hapsatou; Baird, Stephen D; LaCasse, Eric C; Korneluk, Robert G.
Afiliación
  • Beug ST; Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
  • Cheung HH; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
  • Sanda T; Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
  • St-Jean M; Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
  • Beauregard CE; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
  • Mamady H; Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
  • Baird SD; Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
  • LaCasse EC; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
  • Korneluk RG; Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
Sci Signal ; 12(566)2019 01 29.
Article en En | MEDLINE | ID: mdl-30696705
The controlled production and downstream signaling of the inflammatory cytokine tumor necrosis factor-α (TNF-α) are important for immunity and its anticancer effects. Although chronic stimulation with TNF-α is detrimental to the health of the host in several autoimmune and inflammatory disorders, TNF-α-contrary to what its name implies-leads to cancer formation by promoting cell proliferation and survival. Smac mimetic compounds (SMCs), small-molecule antagonists of inhibitor of apoptosis proteins (IAPs), switch the TNF-α signal from promoting survival to promoting death in cancer cells. Using a genome-wide siRNA screen to identify factors required for SMC-to-TNF-α-mediated cancer cell death, we identified the transcription factor SP3 as a critical molecule in both basal and SMC-induced production of TNF-α by engaging the nuclear factor κB (NF-κB) transcriptional pathway. Moreover, the promotion of TNF-α expression by SP3 activity confers differential sensitivity of cancer versus normal cells to SMC treatment. The key role of SP3 in TNF-α production and signaling will help us further understand TNF-α biology and provide insight into mechanisms relevant to cancer and inflammatory disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Factor de Necrosis Tumoral alfa / Materiales Biomiméticos / Factor de Transcripción Sp3 / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Factor de Necrosis Tumoral alfa / Materiales Biomiméticos / Factor de Transcripción Sp3 / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos