Involvement of the Oct-1 regulatory element of the gadd45 promoter in the p53-independent response to ultraviolet irradiation

Cancer Res. 2001 Feb 1;61(3):1187-95.

Abstract

The gadd45 gene, a growth arrest and DNA damage (gadd)-induced gene, is transcriptionally activated by UV irradiation through two distinct pathways. One requires the sequence-specific binding of the p53 tumor suppressor protein to a responsive element within the third intron of the gadd45 gene, and the other is p53-independent activation of the gadd45 promoter region, although the UV-response element that mediates this has yet to be defined. To investigate the sequences involved in induction of gadd45 by UV irradiation in a p53-independent pathway, we performed mutation analyses of the human gadd45 promoter fused to the luciferase reporter gene in cell lines in which p53 was inactivated. We found that the UV-responsive element was involved in the Oct-1 binding site at -99 bp relative to the transcription start site. Electrophoretic mobility shift assays showed that Oct-1, a transcription factor, bound this element on the gadd45 gene, although the intensity and mobility pattern of the retarded bands were not altered by UV irradiation. These results suggest that the Oct-1 regulatory element might be one of the essential elements involved in the activation of the gadd45 promoter by UV irradiation in a p53-independent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / radiation effects
  • Consensus Sequence
  • DNA-Binding Proteins / genetics*
  • Dose-Response Relationship, Radiation
  • Electrophoresis / methods
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Genes, Regulator / radiation effects*
  • HeLa Cells
  • Host Cell Factor C1
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Luciferases / genetics
  • Luciferases / metabolism
  • Octamer Transcription Factor-1
  • Promoter Regions, Genetic / radiation effects*
  • Protein Binding
  • Protein Biosynthesis
  • Proteins / genetics*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transcription Factors / genetics*
  • Transcriptional Activation / radiation effects*
  • Tumor Suppressor Protein p53 / metabolism*
  • Ultraviolet Rays

Substances

  • DNA-Binding Proteins
  • GADD45 protein
  • HCFC1 protein, human
  • Host Cell Factor C1
  • Intracellular Signaling Peptides and Proteins
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Proteins
  • RNA, Messenger
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Luciferases