Glucocorticoid-induced phosphorylation by CDK9 modulates the coactivator functions of transcriptional cofactor GRIP1 in macrophages

• DOI: 10.1038/s41467-017-01569-2
• Publication Date: 2017-11-17T20:22:57Z
• Authors: David A. Rollins; Joubert B. Kharly...; Maddalena Coppo; Bowranigan Tharma...; Sanda Mimouna; Ziyi Guo; Maria A. Sacta; Miles A. Pufall; Robert P. Fisher; Xiaoyu Hu; Yurii Chinenov; Inez Rogatsky
• Keywords: Corepressor; Transrepression

The glucocorticoid (GC) receptor (GR) suppresses inflammation by activating anti-inflammatory and repressing pro-inflammatory genes. GR-interacting protein-1 (GRIP1) is a GR corepressor in macrophages, however, whether GRIP1 mediates GR-activated transcription, what dictates its coactivator versus properties unknown. Here we report that loss macrophages attenuates induction of several targets, GC treatment quiescent globally directs toward binding sites dominated palindromic response elements (GRE), suggesting non-redundant function as coactivator. Interestingly, phosphorylated at an N-terminal serine cluster cyclin-dependent kinase-9 (CDK9), which recruited into GC-induced GR:GRIP1:CDK9 hetero-complexes, producing distinct GRE-specific phospho-isoforms. Phosphorylation potentiates but, remarkably, not properties. Consistently, phospho-GRIP1 CDK9 are detected transrepression near Thus, restricts actions own coregulator via CDK9-mediated phosphorylation to subset