title: The Stress-responsive Gene ATF3 Mediates Dichotomous UV Responses by Regulating the Tip60 and p53 Proteins.
abstract: The response to UV irradiation is important for a cell to maintain its genetic integrity when challenged by environmental genotoxins. An immediate early response to UV irradiation is the rapid induction of activating transcription factor 3 (ATF3) expression. Although emerging evidence has linked ATF3 to stress pathways regulated by the tumor suppressor p53 and the histone acetyltransferase Tip60, the role of ATF3 in the UV response remains largely unclear. Here, we report that ATF3 mediated dichotomous UV responses. Although UV irradiation enhanced the binding of ATF3 to Tip60, knockdown of ATF3 expression decreased Tip60 stability, thereby impairing Tip60 induction by UV irradiation. In line with the role of Tip60 in mediating UV-induced apoptosis, ATF3 promoted the death of p53-defective cells in response to UV irradiation. However, ATF3 could also activate p53 and promote p53-mediated DNA repair, mainly through altering histone modifications that could facilitate recruitment of DNA repair proteins (such as DDB2) to damaged DNA sites. As a result, ATF3 rather protected the p53 wild-type cells from UV-induced apoptosis. Our results thus indicate that ATF3 regulates cell fates upon UV irradiation in a p53-dependent manner.
authors.affiliation: From the Georgia Cancer Center and.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Cui
authors.affiliation: From the Georgia Cancer Center and.
authors.forename: Xingyao
authors.initials: X
authors.lastname: Li
authors.affiliation: the Department of Radiology, Ohio State University, Columbus, Ohio 43210.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Han
authors.affiliation: the Department of Radiology, Ohio State University, Columbus, Ohio 43210.
authors.forename: Qi-En
authors.initials: QE
authors.lastname: Wang
authors.affiliation: the Key Laboratory of Molecular Pharmacology and Drug Evaluation, School of Pharmacy, Yantai University, Yantai 264005, China, and.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.affiliation: From the Georgia Cancer Center and Departments of Pathology and.
authors.forename: Han-Fei
authors.initials: HF
authors.lastname: Ding
authors.affiliation: the Department of Radiation Oncology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: Junran
authors.initials: J
authors.lastname: Zhang
authors.affiliation: From the Georgia Cancer Center and Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, Georgia 30912, cyan@augusta.edu.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Yan
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D045744:Cell Line, Tumor; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004795:Enzyme Stability / Q000235:genetics / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5
keywords: ATF3; DNA damage; DNA repair; UV; apoptosis; histone modifications; p53; stress response