Cyclic AMP Responsive Element Binding Proteins Are Involved in 'Emergency' Granulopoiesis through the Upregulation of CCAAT/Enhancer Binding Protein β.

• 平位, 秀世

• Kamio, Naoka

• Huang, Gang

• Matsusue, Akiko

• Ogino, Shinpei

• Kimura, Nobuhiko

• Satake, Sakiko

• Ashihara, Eishi

• Imanishi, Jiro

• Tenen, Daniel G

• Maekawa, Taira

抄録

In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein α (C/EBPα), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBPβ. In this study, a novel lentivirus-based reporter system was developed to elucidate the molecular switch required for C/EBPβ-dependency. The results demonstrated that two cyclic AMP responsive elements (CREs) in the proximal promoter region of C/EBPβ were involved in the positive regulation of C/EBPβ transcription during granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced differentiation of bone marrow cells. In addition, the transcripts of CRE binding (CREB) family proteins were readily detected in hematopoietic stem/progenitor cells. CREB was upregulated, phosphorylated and bound to the CREs in response to GM-CSF stimulation. Retroviral transduction of a dominant negative CREB mutant reduced C/EBPβ mRNA levels and significantly impaired the proliferation/differentiation of granulocyte precursors, while a constitutively active form of CREB facilitated C/EBPβ transcription. These data suggest that CREB proteins are involved in the regulation of granulopoiesis via C/EBPβ upregulation.

収録刊行物

• PloS one

  PloS one 8 (1), 2013-01-30

  Public Library of Science

詳細情報

• CRID: 1050282810741140480
• NII論文ID: 120005242481
• ISSN: 19326203
• HANDLE: 2433/171145
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles