The role of c‐Jun in controlling the EPAC1‐dependent induction of the SOCS3 gene in HUVECs. Issue 9 (11th March 2014)

• Record Type: Journal Article
• Authors: Wiejak, Jolanta; Dunlop, Julia; Yarwood, Stephen J.
• Is Part Of: FEBS letters. Volume 588:Issue 9(2014)
• Page Start: 1556
• Page End: 1561
• Publication Date: 2014-03-11
• Subjects: Cyclic AMP -- Transcription -- SOCS3 -- EPAC1 -- c-Jun -- AP1; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.02.038
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : The cyclic AMP sensor, EPAC1, activates AP1‐mediated transcription in HUVECs. Correspondingly, induction of the SOCS3 minimal promoter by EPAC1 requires a single AP1 site that constitutively binds phosphorylated (Ser63) c‐Jun in DNA‐pull‐down assays. c‐Jun (Ser63) becomes further phosphorylated following cyclic AMP stimulation and specific activation of protein kinase A (PKA), but not through selective activation of EPAC1. Moreover, despite a requirement for c‐Jun for SOCS3 induction in fibroblasts, phospho‐null c‐Jun (Ser63/73Ala) had little effect on SOCS3 induction by cyclic AMP in HUVECs. AP1 activation and SOCS3 induction by EPAC1 in HUVECs therefore occur independently of c‐Jun phosphorylation on Ser63. Abstract : EPAC1 promotes AP1‐dependent transcription in HUVECs. Delineation of the minimal, EPAC1‐responsive SOCS3 promoter in human cells. Phosphorylated c‐Jun (Ser 63) is constitutively associated with the SOCS3 promoter. Phosphorylation of c‐Jun on Ser63 requires activation of PKA, but not EPAC1. c‐Jun is required for SOCS3 induction by cyclic AMP in MEFs.