RNA helicase A is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus.
Proc Natl Acad Sci U S A
; 107(37): 16125-30, 2010 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-20802156
ABSTRACT
EGF induces the translocation of EGF receptor (EGFR) from the cell surface to the nucleus where EGFR activates gene transcription through its binding to an AT-rich sequence (ATRS) of the target gene promoter. However, how EGFR, without a DNA-binding domain, can bind to the gene promoter is unclear. In the present study, we show that RNA helicase A (RHA) is an important mediator for EGFR-induced gene transactivation. EGF stimulates the interaction of EGFR with RHA in the nucleus of cancer cells. The EGFR/RHA complex then associates with the target gene promoter through binding of RHA to the ATRS of the target gene promoter to activate its transcription. Knockdown of RHA expression in cancer cells abrogates the binding of EGFR to the target gene promoter, thereby reducing EGF/EGFR-induced gene expression. In addition, interruption of EGFR-RHA interaction decreases the EGFR-induced promoter activity. Consistently, we observed a positive correlation of the nuclear expression of EGFR, RHA, and cyclin D1 in human breast cancer samples. These results indicate that RHA is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Ativação Transcricional
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Núcleo Celular
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RNA Helicases
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Receptores ErbB
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article