Ei24, a novel E2F target gene, affects p53-independent cell death upon ultraviolet C irradiation

Young Hoon Sung, Young Jin, Yunhwa Kang, Sushil Devkota, Jaehoon Lee, Jae Il Roh, Han Woong Lee

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The deficiency of retinoblastoma (Rb) gene deregulates E2F transcription factors and thus induces E2F target genes directly or p53 target genes indirectly via mouse p19Arf (or p14ARF in humans), an E2F target gene. Here, we identified that etoposideinduced 2.4 mRNA (Ei24)/p53-induced gene 8 (Pig8), a p53 target gene involved in apoptosis and autophagy, was up-regulated in Rb-/- mouse embryonic fibroblasts (MEFs). The Ei24 promoter was activated by E2F1 via multiple E2F-responsive elements, independently of the previously reported p53-responsive element. Chromatin immunoprecipitation assays revealed that E2F1 directly acts on the mouse Ei24 promoter. We observed that Ei24 expression was suppressed inp53 -/- MEFs upon UVC irradiation, which was exacerbated inp53 -/- E2f1-/- MEFs, supporting the positive role of E2F1 on Ei24 transcription. Furthermore, Ei24 knockdown sensitized p53-/- MEFs against UVC irradiation. Together, our data indicate that Ei24 is a novel E2F target gene contributing to the survival of p53-deficient cells upon UVC irradiation and thus may have a potential significance as a therapeutic target of certain chemotherapy for treating p53-deficient tumors.

Original languageEnglish
Pages (from-to)31261-31267
Number of pages7
JournalJournal of Biological Chemistry
Volume288
Issue number43
DOIs
Publication statusPublished - 2013 Oct 25

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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