Gβγ is a negative regulator of AP-1 mediated transcription

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• 作者：M&#xe9 ; lanie Robitaille ; Sarah Gora ; Ying Wang ; Eug&#xe9 ; nie Goupil ; Darlaine P&#xe9 ; trin ; Danny Del Duca ; Louis R. Villeneuve ; Bruce G. Allen ; St&#xe9 ; phane A. Laporte ; Daniel J. Bernard ; Terence E.
• 关键词：Fos ; G proteins ; Transcription ; Protein fragment complementation ; Signalling
• 刊名：Cellular Signalling
• 出版年：2010
• 出版时间：August 2010
• 年：2010
• 卷：22
• 期：8
• 页码：1254-1266
• 全文大小：807 K

文摘

Following stimulation of G protein-coupled receptors (GPCRs) at the cell surface, heterotrimeric G proteins are activated. Both Gα and Gβγ subunits regulate specific effectors to transmit signals received by the receptor. Recent data suggest potential nuclear localization or translocation of the Gβγ subunit. Here, we show that co-expression of the Gβγ dimer decreased phorbol 12-myristate 13-acetate (PMA)-stimulated AP-1 gene reporter activity in HEK293 cells as well as the AP-1 dependent gonadotropin-releasing hormone-stimulated human follicle-stimulating hormone β reporter activity in LβT2 gonadotrope cells. Further, we identify Fos transcription factors as novel interactors of the Gβ1 subunit, using protein fragment complementation assays, as well as co-immunoprecipitation in vivo and in vitro. Fos proteins dimerize with Jun proteins to form activator protein-1 (AP-1) transcription factor complexes, which regulate target gene expression. Gβγ did not interfere with the dimerization of Fos and Jun or their ability to bind DNA. Rather, Gβγ co-localized with the AP-1 complex in the nucleus and recruited histone deacetylases (HDACs) to inhibit AP-1 transcriptional activity. Our data indicate a novel role for Gβγ subunits as transcriptional regulators.