Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/21156
Título: Two CCAAT/enhancer binding protein sites in the cytochrome P4503A1 locus - Potencial role in the glucocorticoid response
Autor: Rodrigues, E
Vilarem, MJ
Ribeiro, V
Maurel, P
Lechner, MC
Palavras-chave: Biochemistry & Molecular Biology
Data: 2003
Citação: EUROPEAN JOURNAL OF BIOCHEMISTRY. - Vol. 270, n. 3 (FEB 2003), p. 556-564
Resumo: Induction of CYP3A genes by the ligand-activated pregnane-X-receptor (PXR) involves the interaction of other as yet unidentified liver transcription factors. Here we show that the CYP3A1 promoter contains two active sites controlled by the CCAAT/enhancer-binding protein alpha (C/EBPalpha), previously shown to regulate a number of liver stress response genes. We have identified two functional C/EBP binding sites at the CYP3A1 promoter that confer luciferase activity to C/EBPalpha cotransfected CHO cells. When inserted upstream of a thymidine kinase promoter, oligonucleotides corresponding to these elements (-350/-311 and -628/-608), increase reporter gene expression when cotransfected with a C/EBPalpha expression vector. Point mutations in the most conserved nucleotides in either element prevent binding of C/EBPalpha and abolish transactivation of the CYP3A1 promoter. Moreover, we demonstrate that C/EBPalpha accumulates in the rat liver nuclei in response to dexamethasone, and that under these conditions C/EBPalpha binds to the CYP3A1 promoter elements. Our results suggest a correlation between transcription of C/EBPalpha, nuclear protein function and induction of CYP3A1 by dexamethasone in the liver. They also support the notion that C/EBPalpha participates in the up-regulation of the CYP3A1 gene in response to synthetic glucocorticoids.
URI: http://hdl.handle.net/10451/21156
DOI: http://dx.doi.org/10.1046/j.1432-1033.2003.03413.x
ISSN: 0014-2956
Aparece nas colecções:FF - Produção Científica 2000-2009

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