title: Ei24, a novel E2F target gene, affects p53-independent cell death upon ultraviolet C irradiation.
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 p19(Arf) (or p14(ARF) in humans), an E2F target gene. Here, we identified that etoposide-induced 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 in p53(-/-) MEFs upon UVC irradiation, which was exacerbated in p53(-/-) 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.
authors.affiliation: From the Department of Biochemistry, College of Life Science and Biotechnology, and Laboratory Animal Research Center, Yonsei University, Seoul 120-749, Korea and.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Sung
authors.forename: Young
authors.initials: Y
authors.lastname: Jin
authors.forename: Yunhwa
authors.initials: Y
authors.lastname: Kang
authors.forename: Sushil
authors.initials: S
authors.lastname: Devkota
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Lee
authors.forename: Jae-il
authors.initials: JI
authors.lastname: Roh
authors.forename: Han-Woong
authors.initials: HW
authors.lastname: Lee
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D051017:Apoptosis Regulatory Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; C402592:EI24 protein, human; C526185:EI24 protein, mouse; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Cell Death; E2F Transcription Factor; Ei24; Pig8; Retinoblastoma (Rb); Transcription Target Genes; p53