RRC ID 2014
Author Shimokawa T, Ra C.
Title C/EBPalpha functionally and physically interacts with GABP to activate the human myeloid IgA Fc receptor (Fc alphaR, CD89) gene promoter.
Journal Blood
Abstract Human Fcalpha receptor (Fc alphaR; CD89), the receptor for the crystallizable fragment (Fc) of immunoglobulin A (IgA), is expressed exclusively in myeloid cells, including granulocytes and monocytes/macrophages, and is considered to define a crucial role of these cells in immune and inflammatory responses. A 259-base pair fragment of the FCAR promoter is sufficient to direct myeloid expression of a reporter gene and contains functionally important binding sites for CCAAT/enhancer-binding protein alpha (C/EBPalpha) (CE1, CE2, and CE3) and an unidentified Ets-like nuclear protein. Here, we show that the Ets-binding site is bound by a heterodimer composed of GA-binding protein alpha (GABPalpha), an Ets-related factor, and GABPbeta, a Notch-related protein. Cotransfection of GABP increased FCAR promoter activity 3.7-fold through the Ets-binding site. GABP and C/EBPalpha synergistically activated the FCAR promoter 280-fold. Consistent with these observations, in vitro binding analyses revealed a physical interaction between the GABPalpha subunit and C/EBPalpha. This is the first report demonstrating both physical and functional interactions between GABP and C/EBPalpha and will provide new insights into the molecular basis of myeloid gene expression.
Volume 106(7)
Pages 2534-42
Published 2005-10-1
DOI 10.1182/blood-2004-06-2413
PII 2004-06-2413
PMID 15928042
MeSH Antigens, CD / genetics* Antigens, CD / metabolism* Base Sequence Binding Sites CCAAT-Enhancer-Binding Protein-alpha / chemistry CCAAT-Enhancer-Binding Protein-alpha / metabolism* Cell Line Cell Lineage Chromatin Immunoprecipitation DNA / chemistry Electrophoresis, Polyacrylamide Gel Genes, Reporter HeLa Cells Humans Jurkat Cells Models, Genetic Molecular Sequence Data Plasmids / metabolism Promoter Regions, Genetic* Protein Binding Receptors, Fc / genetics* Receptors, Fc / metabolism* Recombinant Fusion Proteins / chemistry Transcription, Genetic Transcriptional Activation Transfection U937 Cells
IF 16.601
Times Cited 10
DNA material pBlue hNF-IL6 (610 Sal I) (RDB01314)