p53-Mediated downregulation of H ferritin promotertranscriptional efficiency via NF-Y

Giovanni Spinelli, Maddalena Di Sanzo, Francesco Costanzo, Salvatore Venuta, Giovanni Cuda, Francesco Baudi, Barbara Quaresima, Maria Concetta Faniello, Giannino Del Sal, Giovanni Morrone

Risultato della ricerca: Articlepeer review

25 Citazioni (Scopus)

Abstract

The tumor suppressor protein p53 triggers many of the cellular responses to DNA damage by regulating the transcription of aseries of downstream target genes. p53 acts on the promoter of the target genes by interacting with the trimeric transcription factorNF-Y. H ferritin promoter activity is tightly dependent on a multiprotein complex called Bbf; on this complex NF-Y plays a majorrole.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 onlythe NF-Y recognition sequence and that the phenomenon is reverted by p53 siRNA; (ii) the p53 C-terminal region is sufficient toelicitate this regulation and that a correct C-terminal acetylation is also required. The H ferritin promoter displays no p53-bindingsites; chromatin immunoprecipitation assays indicate that p53 is recruited on this promoter by NF-Y. The p53–NF-Y interactiondoes 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, thereforeadding a new level of complexity to the regulation of the H ferritin transcription and delineate a role for this protein in a series ofcellular events triggered by p53 activation.
Lingua originaleEnglish
pagine (da-a)2110-2119
Numero di pagine9
RivistaTHE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume40
Stato di pubblicazionePublished - 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

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