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Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma.
Yang, Yibin; Kelly, Priscilla; Shaffer, Arthur L; Schmitz, Roland; Yoo, Hee Min; Liu, Xinyue; Huang, Da Wei; Webster, Daniel; Young, Ryan M; Nakagawa, Masao; Ceribelli, Michele; Wright, George W; Yang, Yandan; Zhao, Hong; Yu, Xin; Xu, Weihong; Chan, Wing C; Jaffe, Elaine S; Gascoyne, Randy D; Campo, Elias; Rosenwald, Andreas; Ott, German; Delabie, Jan; Rimsza, Lisa; Staudt, Louis M.
Afiliación
  • Yang Y; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Kelly P; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Shaffer AL; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Schmitz R; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Yoo HM; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Liu X; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Huang DW; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Webster D; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Young RM; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Nakagawa M; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Ceribelli M; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Wright GW; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yang Y; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Zhao H; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Yu X; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Xu W; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA.
  • Chan WC; Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Jaffe ES; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Gascoyne RD; British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada.
  • Campo E; Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain.
  • Rosenwald A; Department of Pathology, University of Würzburg, 97080 Würzburg, Germany.
  • Ott G; Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, 70376 Stuttgart, Germany.
  • Delabie J; Department of Pathology, University Health Network, Toronto, Ontario M5G 2C4, Canada.
  • Rimsza L; Department of Pathology, University of Arizona, Tucson, AZ 85724, USA.
  • Staudt LM; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 4N115, Bethesda, MD 20892, USA. Electronic address: lstaudt@mail.nih.gov.
Cancer Cell ; 29(4): 494-507, 2016 Apr 11.
Article en En | MEDLINE | ID: mdl-27070702
ABSTRACT
Chronic active B cell receptor (BCR) signaling, a hallmark of the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activate IκB kinase (IKK) and the classical NF-κB pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-κB activity in ABC DLBCL. cIAP1/2 attach K63-linked polyubiquitin chains on themselves and on BCL10, resulting in the recruitment of IKK and the linear ubiquitin chain ligase LUBAC, which is essential for IKK activation. SMAC mimetics target cIAP1/2 for destruction, and consequently suppress NF-κB and selectively kill BCR-dependent ABC DLBCL lines, supporting their clinical evaluation in patients with ABC DLBCL.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo; Linfocitos B/efectos de los fármacos; Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico; Dipéptidos/uso terapéutico; Indoles/uso terapéutico; Proteínas Inhibidoras de la Apoptosis/fisiología; Linfoma de Células B Grandes Difuso/tratamiento farmacológico; Proteínas de Neoplasias/fisiología; Procesamiento Proteico-Postraduccional/efectos de los fármacos; Triazoles/uso terapéutico; Ubiquitina-Proteína Ligasas/fisiología; Animales; Proteínas Reguladoras de la Apoptosis; Proteína 10 de la LLC-Linfoma de Células B; Linfocitos B/metabolismo; Proteína 3 que Contiene Repeticiones IAP de Baculovirus; Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología; Proteínas Adaptadoras de Señalización CARD/metabolismo; Sistemas CRISPR-Cas; Caspasas/metabolismo; Línea Celular Tumoral; Dipéptidos/farmacología; Activación Enzimática; Dosificación de Gen; Perfilación de la Expresión Génica; Regulación Neoplásica de la Expresión Génica/efectos de los fármacos; Guanilato Ciclasa/metabolismo; Humanos; Quinasa I-kappa B/metabolismo; Indoles/farmacología; Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores; Proteínas Inhibidoras de la Apoptosis/genética; Péptidos y Proteínas de Señalización Intracelular/química; Linfoma de Células B Grandes Difuso/clasificación; Linfoma de Células B Grandes Difuso/metabolismo; Ratones; Ratones Endogámicos NOD; Ratones SCID; Proteínas Mitocondriales/química; Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas; Complejos Multiproteicos/metabolismo; FN-kappa B/antagonistas & inhibidores; FN-kappa B/metabolismo; Proteínas de Neoplasias/antagonistas & inhibidores; Proteínas de Neoplasias/genética; Proteínas de Neoplasias/metabolismo; Receptores de Antígenos de Linfocitos B/metabolismo; Triazoles/farmacología; Ubiquitina-Proteína Ligasas/antagonistas & inhibidores; Ubiquitina-Proteína Ligasas/genética; Ubiquitinación/efectos de los fármacos; Ensayos Antitumor por Modelo de Xenoinjerto
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazoles / Linfocitos B / Procesamiento Proteico-Postraduccional / Linfoma de Células B Grandes Difuso / Compuestos Bicíclicos Heterocíclicos con Puentes / Ubiquitina-Proteína Ligasas / Proteínas Adaptadoras Transductoras de Señales / Dipéptidos / Proteínas Inhibidoras de la Apoptosis / Indoles Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazoles / Linfocitos B / Procesamiento Proteico-Postraduccional / Linfoma de Células B Grandes Difuso / Compuestos Bicíclicos Heterocíclicos con Puentes / Ubiquitina-Proteína Ligasas / Proteínas Adaptadoras Transductoras de Señales / Dipéptidos / Proteínas Inhibidoras de la Apoptosis / Indoles Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos