RRC ID 42725
Author Masuda Y, Futamura M, Kamino H, Nakamura Y, Kitamura N, Ohnishi S, Miyamoto Y, Ichikawa H, Ohta T, Ohki M, Kiyono T, Egami H, Baba H, Arakawa H.
Title The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage.
Journal J Hum Genet
Abstract The tumor suppressor p53 plays a crucial role in the cellular response to DNA damage by transcriptional activation of numerous downstream genes. Although a considerable number of p53 target genes have been reported, the precise mechanism of p53-regulated tumor suppression still remains to be elucidated. Here, we report a novel role of the DFNA5 gene in p53-mediated etoposide-induced cell death. The DFNA5 gene has been previously reported to be responsible for autosomal-dominant, nonsyndromic hearing impairment. The expression of the DFNA5 gene was strongly induced by exogenous and endogenous p53. The chromatin immunoprecipitation assay indicated that a potential p53-binding sequence is located in intron 1 of the DFNA5 gene. Furthermore, the reporter gene assay revealed that the sequence displays p53-dependent transcriptional activity. The ectopic expression of DFNA5 enhanced etoposide-induced cell death in the presence of p53; however, it was inhibited in the absence of p53. Finally, the expression of DFNA5 mRNA was remarkably induced by gamma-ray irradiation in the colon of p53(+/+) mice but not in that of p53(-/-) mice. These results suggest that DFNA5 plays a role in the p53-regulated cellular response to genotoxic stress probably by cooperating with p53.
Volume 51(8)
Pages 652-664
Published 2006-1-1
DOI 10.1007/s10038-006-0004-6
PII 10.1007/s10038-006-0004-6
PMID 16897187
MeSH Animals Apoptosis / drug effects Base Sequence Binding Sites / drug effects COS Cells Chlorocebus aethiops DNA Damage* Etoposide / pharmacology Exons / genetics Gene Expression Regulation, Neoplastic / drug effects Genome, Human / genetics Hearing Loss / genetics* Humans Mice Microarray Analysis Molecular Sequence Data Protein Transport / drug effects RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Estrogen / genetics Receptors, Estrogen / metabolism* Transcription, Genetic / drug effects Tumor Cells, Cultured Tumor Suppressor Protein p53 / metabolism*
IF 2.831
Human and Animal Cells