| RRC ID |
42725
|
| 著者 |
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.
|
| タイトル |
The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage.
|
| ジャーナル |
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.
|
| 巻・号 |
51(8)
|
| ページ |
652-664
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
|
