Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53.
Interferon regulatory factors (IRFs) regulate transcription of interferon genes through DNA sequence-specific binding to these targets. Using a differential display method for examining gene expression in p53-defective cells infected with adenovirus containing wild-type p53, we found that expression of interferon regulatory factor 5 (IRF-5) mRNA was increased in the presence of exogenous p53. An electrophoretic mobility-shift assay showed that a potential p53 binding site (p53BS) detected in exon 2 of the IRF-5 gene could in fact bind to p53 protein. Moreover, a heterologous reporter assay revealed that the p53BS possessed p53-dependent transcriptional activity. Expression of IRF-5 was induced in p53+/+ cells (MCF7 and NHDF), but not inp53-/- cells (H1299) when DNA was damaged by gamma-irradiation, UV-radiation, or adriamycin treatment in a wild-type p53-dependent manner. These results suggest that IRF-5 is a novel p53-target, and that it might mediate the p53-dependent immune response.
Mori
Toshiki
T
Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Anazawa
Yoshio
Y
Iiizumi
Megumi
M
Fukuda
Seisuke
S
Nakamura
Yusuke
Y
Arakawa
Hirofumi
H
D000595:Amino Acid Sequence; D001665:Binding Sites; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D050835:Interferon Regulatory Factors; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53