Novel Function of Transcription Factor ATF5: Blockade of p53-dependent Apoptosis Induced by Ionizing Irradiation

Cell Structure and Function

Kenichiro Shibata¹  Yusuke Miyai²  Takeshi Nishioka³  Hiroki Shirato⁴  Akihiro Homma⁵  Hisashi Haga²  Motoaki Yasuda¹  Kazushige Kawabata² 

[1] Department of Oral Pathobiology, Graduate School of Dental Medicine, Hokkaido University;Division of Biological Sciences, Graduate School of Science, Hokkaido University;Department of Biomedical Sciences and Engineering, Faculty of Health Sciences, Graduate School of Health Sciences, Hokkaido University;Department of Radiology, Graduate School of Medicine, Hokkaido University;Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Hokkaido University

关键词: ATF5;    p53;    apoptosis;    radiotherapy;    cell motility;   

DOI  :  10.1247/csf.08041

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(15)Cited-By(3)Purpose: To find a new molecule that affects p53-dependent radiosensitivity. Methods and Materials: A mouse sarcoma cell line, QRsP(p53+/+), was used. From this cell line, we established a radiosensitive clone and a radioresistant one. Colony assay, p53 gene transfer, a luciferase assay for p53 and p21, animal transplantation experiment, and DNA array analyses were performed. Results: Microarray showed marked reduction of a transcription factor, ATF5, both in vitro and in vivo for the radiosensitive clone. Interestingly, flow cytometric analysis demonstrated marked apoptosis for the radiosensitive clone by p53 cloned adenovirus infection. Luciferase reporter assay revealed that ATF5 suppressed the transactivational activity of p53 and p63. By ATF5 gene transfer, the radiosensitive clone regained resistance to both ionizing-radiation and Ad-p53 infection-induced cell death. Surprisingly, time-lapse cell migration observation revealed greater cell motility for ATF5-transfected radiosensitive clone. Conclusions: It seems likely that ATF5 is a potent repressor of p53 and elevated expression of ATF5 in a tumor may relate to enhanced malignant phenotypes, such as radioresistance or greater cell motility.

【 授权许可】

Unknown