Radiation signaling mediated by Jun activation following dissociation from a cell type-specific repressor

Dennis E. Hallahan*, David Gius, Jaya Kuchibhotla, Vikas Sukhatme, Donald W. Kufe, Ralph R. Weichselbaum

*Corresponding author for this work

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The promoter regions of several radiation-inducible genes contain AP-1 cis-acting regulatory elements that are dependent upon protein kinase C signaling. We analyzed nuclear protein from irradiated human tumor cell lines for binding to the AP-1 consensus sequence. The increase in nuclear protein binding following irradiation was specific for the AP-1 sequence and was reduced by antibodies to c-Jun and c-Fos. The AP-1 DNA binding sequence was found to regulate transcription in irradiated cells and mutation of the AP-1 site within the c-jun promoter abolished transcriptional induction by radiation. The gene encoding the chimeric transcription factor Gal4-Jun5- 253, which includes the DNA binding region of Gal4 and the transcriptional regulatory region of c-Jun, was cotransfected with the reporter plasmid with Gal4 binding sequences (G5B-CAT). Transfection of RIT-3 and HeLa cells revealed that the regulatory region of Jun was sufficient to activate transcription following irradiation. Conversely, Hep G2 cells, which do not contain the cell type-specific Jun repressor, were not responsive to radiation-induced Jun activation. The c-Jun repressor was found to regulate Jun activation by experiments using the expression vector CMV-jun, which competes for Jun inhibitor and eliminates radiation-induction of Jun. We propose transcription factor dissociation from inhibitor proteins may participate in the initiation of cellular responses to ionizing radiation.

Original languageEnglish (US)
Pages (from-to)4903-4907
Number of pages5
JournalJournal of Biological Chemistry
Volume268
Issue number7
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hallahan, D. E., Gius, D., Kuchibhotla, J., Sukhatme, V., Kufe, D. W., & Weichselbaum, R. R. (1993). Radiation signaling mediated by Jun activation following dissociation from a cell type-specific repressor. Journal of Biological Chemistry, 268(7), 4903-4907.