A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription.
Cell
; 123(5): 833-47, 2005 Dec 02.
Article
em En
| MEDLINE
| ID: mdl-16325578
ABSTRACT
Chromatin modification is considered to be a fundamental mechanism of regulating gene expression to generate coordinated responses to environmental changes, however, whether it could be directly regulated by signals mediated by G protein-coupled receptors (GPCRs), the largest surface receptor family, is not known. Here, we show that stimulation of delta-opioid receptor, a member of the GPCR family, induces nuclear translocation of beta-arrestin 1 (betaarr1), which was previously known as a cytosolic regulator and scaffold of GPCR signaling. In response to receptor activation, betaarr1 translocates to the nucleus and is selectively enriched at specific promoters such as that of p27 and c-fos, where it facilitates the recruitment of histone acetyltransferase p300, resulting in enhanced local histone H4 acetylation and transcription of these genes. Our results reveal a novel function of betaarr1 as a cytoplasm-nucleus messenger in GPCR signaling and elucidate an epigenetic mechanism for direct GPCR signaling from cell membrane to the nucleus through signal-dependent histone modification.
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Histonas
/
Núcleo Celular
/
Regulação da Expressão Gênica
/
Receptores Opioides delta
/
Arrestinas
/
Receptores Acoplados a Proteínas G
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article