Ionizing radiation-inducible apoptosis in the absence of p53 linked to transcription factor EGR-1

Mansoor M. Ahmed, Stephen F. Sells, Kolaparthi Venkatasubbarao, Sana M. Fruitwala, Sumathi Muthukkumar, Cindy Harp, Mohammed Mohiuddin, Vivek M. Rangnekar

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

The tumor suppressor protein p53 is a pivotal regulator of apoptosis, and prostate cancer cells that lack p53 protein are moderately resistant to apoptotic death by ionizing radiation. Genes encoding the transcription factor early growth response-1 (EGR-1) and cytokine tumor necrosis factor-α (TNF-α) were induced upon irradiation of prostate cancer cells, and inhibition of EGR-1 function resulted in abrogation of both TNF-α induction and apoptosis. Induction of the TNF-α gene by ionizing radiation and EGR-1 was mediated via a GC-rich EGR-1-binding motif in the TNF-α promoter. Because TNF-α induces apoptosis in prostate cancer cells, these findings suggest that, in the absence of p53, ionizing radiation-inducible apoptosis is mediated by EGR-1 via TNF-α transactivation.

Original languageEnglish (US)
Pages (from-to)33056-33061
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number52
DOIs
StatePublished - Dec 26 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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