p53-mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y.
Int J Biochem Cell Biol
; 40(10): 2110-9, 2008.
Article
em En
| MEDLINE
| ID: mdl-18372207
ABSTRACT
The tumor suppressor protein p53 triggers many of the cellular responses to DNA damage by regulating the transcription of a series of downstream target genes. p53 acts on the promoter of the target genes by interacting with the trimeric transcription factor NF-Y. H ferritin promoter activity is tightly dependent on a multiprotein complex called Bbf; on this complex NF-Y plays a major role. The aim of this work was to study the modulation of H ferritin expression levels by p53. CAT reporter assays indicate that (i) p53 overexpression strongly downregulates the transcriptional efficiency driven by an H ferritin promoter construct containing only the NF-Y recognition sequence and that the phenomenon is reverted by p53 siRNA; (ii) the p53 C-terminal region is sufficient to elicitate this regulation and that a correct C-terminal acetylation is also required. The H ferritin promoter displays no p53-binding sites; chromatin immunoprecipitation assays indicate that p53 is recruited on this promoter by NF-Y. The p53-NF-Y interaction does not alter the NF-Y DNA-binding ability as indicated by electrophoretic mobility shift assay (EMSA) analysis. These results demonstrate that the gene coding for the H ferritin protein belongs to the family of p53-regulated genes, therefore adding a new level of complexity to the regulation of the H ferritin transcription and delineate a role for this protein in a series of cellular events triggered by p53 activation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apoferritinas
/
Transcrição Gênica
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Regulação para Baixo
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Proteína Supressora de Tumor p53
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Regiões Promotoras Genéticas
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Fator de Ligação a CCAAT
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article