{beta}-Arrestin-1 inhibits glucocorticoid receptor turnover and alters glucocorticoid signaling [Signal Transduction]

In this study, we discovered a novel protein interaction between the glucocorticoid receptor and β-arrestin-1, a scaffold protein with a well-established role in G protein–coupled receptor signaling. Using co-immunoprecipitation and in situ proximity ligation assays in A549 cells, we observed that β-arrestin-1 and unliganded GR interact in the cytoplasm and that, following glucocorticoid binding, the protein complex is found in the nucleus. We show that siRNA-mediated β-arrestin-1 knockdown alters GR protein turnover by up-regulating the E3 ubiquitin ligase Pellino-1, which catalyzes GR ubiquitination and thereby marks the receptor for proteasomal degradation. The enhanced GR turnover observed in β-arrestin-1–deficient cells limits the duration of the glucocorticoid response on GR target genes. These results demonstrate that β-arrestin-1 is a crucial player for the stability of the glucocorticoid receptor. The GR/β-arrestin-1 interaction uncovered here may help unravel mechanisms that contribute to the cell type–specific activities of glucocorticoids.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Signal Transduction Source Type: research