Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2.
Mol Endocrinol
; 15(2): 241-54, 2001 Feb.
Article
em En
| MEDLINE
| ID: mdl-11158331
ABSTRACT
ASC-2 is a recently isolated transcriptional cointegrator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors, AP-1, nuclear factor kappaB (NFkappaB), serum response factor (SRF), and numerous other transcription factors. ASC-2 contained two nuclear receptor-interaction domains, both of which are dependent on the integrity of their core LXXLL sequences. Surprisingly, the C-terminal LXXLL motif specifically interacted with oxysterol receptor LXRss, whereas the N-terminal motif bound a broad range of nuclear receptors. These interactions appeared to be essential because a specific subregion of ASC-2 including the N- or C-terminal LXXLL motif acted as a potent dominant negative mutant with transactivation by appropriate nuclear receptors. In addition, the autonomous transactivation domain (AD) of ASC-2 was found to consist of three separable subregions; i.e. AD1, AD2, and AD3. In particular, AD2 and AD3 were binding sites for CREB binding protein (CBP), and CBP-neutralizing E1A repressed the autonomous transactivation function of ASC-2. Furthermore, the receptor transactivation was not enhanced by ASC-2 in the presence of E1A and significantly impaired by overexpressed AD2. From these results, we concluded that ASC-2 directly binds to nuclear receptors and recruits CBP to mediate the nuclear receptor transactivation in vivo.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas Nucleares
/
Ativação Transcricional
/
Transativadores
/
Receptores Citoplasmáticos e Nucleares
/
Peptídeos e Proteínas de Sinalização Intracelular
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Endocrinol
Assunto da revista:
BIOLOGIA MOLECULAR
/
ENDOCRINOLOGIA
Ano de publicação:
2001
Tipo de documento:
Article