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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2534-2542.
Prepublished online as a Blood First Edition Paper on May 31, 2005; DOI 10.1182/blood-2004-06-2413.
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PHAGOCYTES
C/EBP functionally and physically interacts with GABP to activate the human myeloid IgA Fc receptor (Fc R, CD89) gene promoter
Toshibumi Shimokawa, and
Chisei Ra
From the Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, Tokyo, Japan.
Human Fc receptor (Fc R; 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 (C/EBP ) (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 (GABP ), an Ets-related factor, and GABP , a Notch-related protein. Cotransfection of GABP increased FCAR promoter activity 3.7-fold through the Ets-binding site. GABP and C/EBP synergistically activated the FCAR promoter 280-fold. Consistent with these observations, in vitro binding analyses revealed a physical interaction between the GABP subunit and C/EBP . This is the first report demonstrating both physical and functional interactions between GABP and C/EBP and will provide new insights into the molecular basis of myeloid gene expression. (Blood. 2005;106:2534-2542)

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