title: DNA damage-induced RORα is crucial for p53 stabilization and increased apoptosis.
abstract: A critical component of the DNA damage response is the p53 tumor suppressor, and aberrant p53 function leads to uncontrolled cell proliferation and malignancy. Several molecules have been shown to regulate p53 stability; however, genome-wide systemic approaches for determining the affected, specific downstream target genes have not been extensively studied. Here, we first identified an orphan nuclear receptor, RORα, as a direct target gene of p53, which contains functional p53 response elements. The functional consequences of DNA damage-induced RORα are to stabilize p53 and activate p53 transcription in a HAUSP/Usp7-dependent manner. Interestingly, microarray analysis revealed that RORα-mediated p53 stabilization leads to the activation of a subset of p53 target genes that are specifically involved in apoptosis. We further confirmed that RORα enhances p53-dependent, in vivo apoptotic function in the Drosophila model system. Together, we determined that RORα is a p53 regulator that exerts its role in increased apoptosis via p53.
authors.affiliation: Department of Biological Sciences, Creative Research Initiative Center for Chromatin Dynamics, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Hyunkyung
authors.initials: H
authors.lastname: Kim
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Gina
authors.initials: G
authors.lastname: Lee
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Bhin
authors.forename: Se Kyu
authors.initials: SK
authors.lastname: Oh
authors.forename: Kyeongkyu
authors.initials: K
authors.lastname: Kim
authors.forename: Ki Eun
authors.initials: KE
authors.lastname: Pyo
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lee
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Yim
authors.forename: Keun Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Jongkyeong
authors.initials: J
authors.lastname: Chung
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004249:DNA Damage; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D055550:Protein Stability; D020218:Response Elements / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D016159:Tumor Suppressor Protein p53; D043222:Ubiquitin Thiolesterase