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Transcriptional Activation of Regulator of G Protein Signaling 4 (RGS4) by Inverted CCAAT Box Element (ICE) Binding Factor NF‐YA Attenuates G Protein Signaling
Author(s) -
Yang Jianqi,
Huang Jie,
Chatterjee Tapan K.,
Twait Erik,
Fisher Rory A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.495.16
Subject(s) - transcription factor , biology , caat box , microbiology and biotechnology , signal transduction , transcriptional regulation , promoter , gene expression , gene , genetics
RGS4 is a member of a family of proteins that play critical roles in attenuating GPCR signaling. Enriched in brain, RGS4 is linked to several pathologies, including Parkinson's disease. However, the mechanisms underlying regulation of RGS4 expression have not been studied. Here, we elucidated these mechanisms in PC6 cells, in which RGS4 is induced markedly at cellular confluence. Using gene promoter analyses, we demonstrated that an ICE in the human RGS4 promoter was required for transcriptional activation of RGS4 . Phylogenetic analysis revealed that the ICE was one of four conserved transcription factor binding sites. Functionally, the ICE interacted with NF‐YA, an ICE binding transcription factor, in EMSA and biotin‐labeled DNA oligo pull‐down assays. Exogenous expression of NF‐YA or C/EBPβ activated the RGS4 promoter, while dominant negative NF‐YA and C/EBPβ significantly reduced RGS4 promoter activity. Furthermore, both cyclin D1 and phosphorylated Rb were decreased in confluent cells, indicating cell growth arrest. However, growth arrest induced by serum withdrawal alone did not alter RGS4 expression. Consistent with the fact that RGS4 is a GAP for Gαi and Gαq, LPA‐induced activation of MAPK was attenuated in confluent cells. We conclude that transcriptional activation of RGS4 by NF‐YA leads to an attenuation of G‐protein signaling. Supported by grants from the NIH (GM075033) and AHA (0750057Z).