Cyclic AMP Responsive Element Binding Proteins Are Involved in ‘Emergency’ Granulopoiesis through the Upregulation of CCAAT-Enhancer Binding Protein βReportar como inadecuado




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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.



Autor: Hideyo Hirai , Naoka Kamio, Gang Huang, Akiko Matsusue, Shinpei Ogino, Nobuhiko Kimura, Sakiko Satake, Eishi Ashihara, Jiro Imani

Fuente: http://plos.srce.hr/



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