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RGS13 suppresses CREB‐dependent gene transcription
Author(s) -
Xie Zhihui,
Johnson Eric J,
Druey Kirk M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.782.9
Subject(s) - creb , coactivator , cyclic amp response element binding protein , microbiology and biotechnology , transcription factor , creb binding protein , creb1 , response element , repressor , transcription (linguistics) , activating transcription factor , biology , chemistry , gene expression , gene , promoter , genetics , linguistics , philosophy
cAMP response element binding protein (CREB) promotes transcription of genes involved in neuronal development, metabolism, and immunity. Norepinephrine (NE) secreted into lymphoid organs stimulates Gαs‐coupled β 2 ‐adrenergic receptors on B lymphocytes, leading to CREB‐dependent transcription of the Oct 2 coactivator (OCA‐B). R egulator of G protein S ignalling (RGS) proteins attenuate GPCR signaling by inhibiting Gαi and Gαq but not Gαs. We show that B‐cell‐enriched RGS13 is a direct transcriptional repressor of CREB. Phosphorylation of CREB induced RGS13 nuclear translocation, where it bound pCREB and inhibited CREB‐DNA contact. RGS13 abundance affected pCREB promoter occupancy and CREB target gene transcription in HEK293T cells. Two discontinuous sites on RGS13 (aa15‐33 and aa93‐117) were required for CREB binding and inhibition of CREB activity, which depended on Arg13, Glu15, and Ser104 within these two regions. RGS13 interacted with the kinase‐inducible domain (KID) of CREB, which required the α‐helical conformation of KID induced by CBP binding. Rgs13 −/– B cells exhibited increased β 2 AR‐stimulated pCREB‐DNA binding and OCA‐B expression. Thus, RGS13 may impact humoral immune responses under sympathetic neural control and other physiological responses mediated by CREB.