Induction of a Cell Stress Response Gene RTP801 by DNA Damaging Agent Methyl Methanesulfate Through CCAA/Enhancer Binding Protein

Details

• Personal Author:
  Chen Y ; Lin L ; Qian Y ; Shi X
• Description:
  RTP801 is a newly discovered stress response gene that is induced by hypoxia and other cell stress signals. Here, we investigated the mechanism by which a DNA damaging agent, methyl methanesulfonate (MMS), induces RTP801 transcription. In HaCaT human keratinocytes, MMS was able to induce a rapid increase in the mRNA level of RTP801. Correspondingly, MMS treatment was capable of stimulating a 2.5 kb RTP801 promoter. Deletion studies with the promoter demonstrated a critical region between -1057 and -981 bp of the promoter that is responsive to MMS treatment. Point mutations of the consensus Elk-1 and C/EBP sites within this region were able to abrogate the stimulatory effect of MMS, indicating that Elk-1 and C/EBP are both involved in the transcriptional regulation of the RTP801 gene by MMS. Furthermore, a gel mobility shift assay revealed that MMS was able to initiate rapid formation of a protein complex that bound the C/EBP site of the promoter. In addition, an anti-C/EBPbetaantibody was capable of further shifting the bound protein complex. Therefore, these studies indicate that RTP801 is a transcriptional target of MMS in human keratinocytes and that C/EBP is implicated in transcriptional control of the gene. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured DNA Genetics Occupational Health Safety
• Keywords:
  Cell-cultures DNA-damage Genes Genotoxic-effects Proteins Stress
• ISSN:
  0006-2960
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Indiana ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  44
• Issue:
  10
• NIOSHTIC Number:
  nn:20026394
• Citation:
  Biochemistry 2005 Mar; 44(10):3909-3914
• Email:
  ychen3@iupui.edu
• Federal Fiscal Year:
  2005
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7056f1af192fce26455eaa03ae56f8eabbbf535fb34c4b5fcc50b5d5fc3051fc717bfec09576e4bb27eee9f4c2f7584f60201909b41df13944f5df1b1edf1342
• Download URL:
  https://stacks.cdc.gov/view/cdc/197267/cdc_197267_DS1.pdf
• File Type:
  [PDF - 132.31 KB ]