Reference - Detail
| 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 |
| Altmetric score |
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| The most frequently cited source | Wikipedia |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | |