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The transcription factor XBP1 is selectively required for eosinophil differentiation.
Bettigole, Sarah E; Lis, Raphael; Adoro, Stanley; Lee, Ann-Hwee; Spencer, Lisa A; Weller, Peter F; Glimcher, Laurie H.
Afiliação
  • Bettigole SE; 1] Program in Immunology, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA. [3] Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College, New York, New York, USA.
  • Lis R; 1] Ansary Stem Cell Institute, Department of Genetic Medicine, and Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA. [2] Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York, USA.
  • Adoro S; 1] Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA. [2] Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College, New York, New York, USA.
  • Lee AH; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA.
  • Spencer LA; Department of Medicine, Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
  • Weller PF; Department of Medicine, Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
  • Glimcher LH; 1] Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA. [2] Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College, New York, New York, USA.
Nat Immunol ; 16(8): 829-37, 2015 Aug.
Article em En | MEDLINE | ID: mdl-26147683
The transcription factor XBP1 has been linked to the development of highly secretory tissues such as plasma cells and Paneth cells, yet its function in granulocyte maturation has remained unknown. Here we discovered an unexpectedly selective and absolute requirement for XBP1 in eosinophil differentiation without an effect on the survival of basophils or neutrophils. Progenitors of myeloid cells and eosinophils selectively activated the endoribonuclease IRE1α and spliced Xbp1 mRNA without inducing parallel endoplasmic reticulum (ER) stress signaling pathways. Without XBP1, nascent eosinophils exhibited massive defects in the post-translational maturation of key granule proteins required for survival, and these unresolvable structural defects fed back to suppress critical aspects of the transcriptional developmental program. Hence, we present evidence that granulocyte subsets can be distinguished by their differential reliance on secretory-pathway homeostasis.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Expressão Gênica / Diferenciação Celular / Proteínas de Ligação a DNA / Eosinófilos Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Expressão Gênica / Diferenciação Celular / Proteínas de Ligação a DNA / Eosinófilos Idioma: En Ano de publicação: 2015 Tipo de documento: Article