The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage

被引：102

作者：

Masuda Y. ^{[1
,5
]}

Futamura M. ^{[1
]}

Kamino H. ^{[1
]}

Nakamura Y. ^{[1
]}

Kitamura N. ^{[1
]}

Ohnishi S. ^{[1
]}

Miyamoto Y. ^{[1
]}

Ichikawa H. ^{[2
]}

Ohta T. ^{[3
]}

Ohki M. ^{[3
]}

Kiyono T. ^{[4
]}

Egami H. ^{[5
]}

Baba H. ^{[5
]}

Arakawa H. ^{[1
]}

机构：

[1] Cancer Medicine and Biophysics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045

[2] Cancer Transcriptome Project, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045

[3] Center for Medical Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045

[4] Virology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045

[5] Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto 860-8556

来源：

Journal of Human Genetics | 2006年 / 51卷 / 8期

关键词：

Apoptosis; Cell death; DNA damage; Etoposide; Hearing impairment; p53; p53 target gene; Tumor suppressor gene;

D O I：

10.1007/s10038-006-0004-6

中图分类号：

学科分类号：

摘要：

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. © The Japan Society of Human Genetics and Springer-Verlag 2006.

引用

页码：652 / 664

页数：12

共 36 条

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