Abstract
Abstract Regulators of G-protein Signaling (RGS) proteins negatively regulate GPCRs by accelerating the GTPase activity of Gα. In recent years, non-GPCR-related functions have also been described for these proteins. We found previously that RGS13 was enriched in mast cells and inhibited anaphylaxis in mice by suppressing IgE-mediated mast cell degranulation. We therefore examined the transcriptional regulation of RGS13 in mast cells. We confirmed the transcriptional start site (TSS) by 5’ RACE in cDNA from the human mast cell line LAD2 and demonstrated promoter activity in a ~ 1 kb element upstream of exon 1 using luciferase reporter assays. We also identified 2 potential p53 response elements (RE) in the region 2 kb upstream of the TSS by bioinformatic analysis. Overexpression and shRNA-mediated knockdown of endogenous p53 in LAD2 cells revealed an inverse relationship between p53 levels and RGS13 expression. Endogenous p53 in these cells bound exclusively to oligonucleotides containing the p53 RE most upstream of the TSS. Cells expressing double-stranded oligonucleotides containing this site or a p53 consensus site had enhanced promoter activity. These studies indicate that p53 suppresses RGS13 transcription in mast cells. Thus, upregulation of p53 activity in mast cells exposed to stress could reduce the threshold for degranulation as a result of decreased RGS13 expression.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
