title: Novel function of transcription factor ATF5: blockade of p53-dependent apoptosis induced by ionizing irradiation.
abstract: OBJECTIVE
  To find a new molecule that affects p53-dependent radiosensitivity.
  
  
  METHODS
  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.
authors.affiliation: Department of Biomedical Sciences and Engineering, Faculty of Health Sciences, Graduate School of Health Sciences, Hokkaido University, Sapporo, Japan. trout@hs.hokudai.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishioka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Miyai
authors.forename: Hisashi
authors.initials: H
authors.lastname: Haga
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kawabata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirato
authors.forename: Akihiro
authors.initials: A
authors.lastname: Homma
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Shibata
authors.forename: Motoaki
authors.initials: M
authors.lastname: Yasuda
mesh_terms: D051696:Activating Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D051696:Activating Transcription Factors; C471855:Atf5 protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D016159:Tumor Suppressor Protein p53