p53-mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y.
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.
Faniello
Maria Concetta
MC
Dipartimento di Medicina Sperimentale e Clinica "G. Salvatore", Università di Catanzaro "Magna Graecia", Campus Universitario, Germaneto, 88100 Catanzaro, Italy.
Di Sanzo
Maddalena
M
Quaresima
Barbara
B
Baudi
Francesco
F
Di Caro
Valentina
V
Cuda
Giovanni
G
Morrone
Giovanni
G
Del Sal
Giannino
G
Spinelli
Giovanni
G
Venuta
Salvatore
S
Costanzo
Francesco
F
D001052:Apoferritins / Q000235:genetics*; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D023081:CCAAT-Binding Factor; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D001052:Apoferritins; D050880:p300-CBP Transcription Factors