Pbx1 is a co-factor for Cdx-2 in regulating proglucagon gene expression in pancreatic A cells

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:249

Article

Liu, T ; Branch, DR ; Jin, TR

关键词: proglucagon;    Cdx-2;    Pbx1;    homeobox gene;    GST pull down;   

DOI  :  10.1016/j.mce.2006.02.007

来源: Elsevier

【 摘 要 】

A number of Hox and Hox-like homeodomain (HD) proteins have been previously shown to utilize members of the TALE HD protein family as co-factors in regulating gene expression. The caudal HD protein Cdx-2 is a transactivator for the proglucagon gene, expressed in pancreatic A cells and intestinal endocrine L cells. We demonstrate here that co-transfection of the TALE homeobox gene Pbx1 enhanced the activation of Cdx-2 on the proglucagon promoter in either the pancreatic A cell line InR1-G9 or BHK fibroblasts. The activation was observed for proglucagon promoter constructs with or without the binding motifs for Pbx1. Furthermore, mutating the penta-peptide motif (binding motif for TALE HD proteins) on Cdx-2 substantially attenuated its activation on proglucagon promoter, but not on the sucrase-isomaltase gene (SI) promoter, or its own (Cdx-2) promoter; suggesting that Cdx-2 utilizes Pbx1 as a co-factor for regulating the expression of selected target genes. Physical interaction between Cdx-2 and Pbx1 was demonstrated by co-immunoprecipitation as well as GST fusion protein pull-down. We suggest that this study reveals a novel function for Pbx1 in pancreatic islet physiology: regulating proglucagon expression by serving as a co-factor for Cdx-2. (c) 2006 Elsevier Ireland Ltd. All fights reserved.

【 授权许可】

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