Protein phosphatase 1 alpha enhances glucocorticoid receptor activity by a mechanism involving phosphorylation of serine-211. (1st December 2020)

• Record Type: Journal Article
• Authors: Patt, Melanie; Gysi, Joël; Faresse, Nourdine; Cidlowski, John A.; Odermatt, Alex
• Is Part Of: Molecular and cellular endocrinology. Volume 518(2020)
• Publication Date: 2020-12-01
• Subjects: Glucocorticoid receptor -- Protein phosphatase 1 alpha -- Glycogen synthase kinase 3 -- Phosphorylation -- Signaling; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2020.110873
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: By acting as a ligand-dependent transcription factor the glucocorticoid receptor (GR) mediates the actions of glucocorticoids and regulates many physiological processes. An impaired regulation of glucocorticoid action has been associated with numerous disorders. Thus, the elucidation of underlying signaling pathways is essential to understand mechanisms of disrupted glucocorticoid function and contribution to diseases. This study found increased GR transcriptional activity upon overexpression of protein phosphatase 1 alpha (PP1α) in HEK-293 cells and decreased expression levels of GR-responsive genes following PP1α knockdown in the endogenous A549 cell model. Mechanistic investigations revealed reduced phosphorylation of GR-Ser211 following PP1α silencing and provided a first indication for an involvement of glycogen synthase kinase 3 (GSK-3). Thus, the present study identified PP1α as a novel post-translational activator of GR signaling, suggesting that disruption of PP1α function could lead to impaired glucocorticoid action and thereby contribute to diseases. Highlights: PP1α is a novel post-translational activator of GR signaling. PP1α modulates GR-Ser211 phosphorylation levels. The PP1α-dependent GR activation potentially involves GSK-3.