RGS13 acts as a nuclear repressor of CREB.
Mol Cell
; 31(5): 660-70, 2008 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-18775326
ABSTRACT
Cyclic AMP-induced phosphorylation of the transcription factor CREB elicits expression of genes mediating diverse biological functions. In lymphoid organs, the neurotransmitter norepinephrine stimulates beta(2)-adrenergic receptors on B lymphocytes to promote CREB-dependent expression of genes like the B cell Oct 2 coactivator (OCA-B). Although CREB phosphorylation recruits cofactors such as CBP/p300 to stimulate transcription, bona fide endogenous inhibitors of CREB-coactivator or CREB-DNA interactions have not emerged. Here, we identified RGS13, a member of the Regulator of G protein Signaling (RGS) protein family, as a nuclear factor that suppresses CREB-mediated gene expression. cAMP or Ca(2+) signaling promoted RGS13 accumulation in the nucleus, where it formed a complex with phosphorylated CREB and CBP/p300. RGS13 reduced the apparent affinity of pCREB for both the CRE and CBP. B lymphocytes from Rgs13(-/-) mice had more beta(2)-agonist-induced OCA-B expression. Thus, RGS13 inhibits CREB-dependent transcription of target genes through disruption of complexes formed at the promoter.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Núcleo Celular
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Regulação da Expressão Gênica
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Proteínas RGS
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell
Ano de publicação:
2008
Tipo de documento:
Article