title: The activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 to the distal CCAAT box of the RhoB promoter.
abstract: The Ras-related small GTP-binding protein RhoB is rapidly induced in response to genotoxic stresses caused by ionizing radiation. It is known that UV-induced RhoB expression results from the binding of activating transcription factor 2 (ATF2) via NF-Y to the inverted CCAAT box (-23) of the RhoB promoter. Here, we show that the association of c-Jun with the distal CCAAT box (-72) is primarily involved in UV-induced RhoB expression and p38 MAPK regulated RhoB induction through the distal CCAAT box. UV-induced RhoB expression and apoptosis were markedly attenuated by pretreatment with the p38 MAPK inhibitor. siRNA knockdown of RhoB, ATF2 and c-Jun resulted in decreased RhoB expression and eventually restored the growth of UV-irradiated Jurkat cells. In the reporter assay using luciferase under the RhoB promoter, inhibition of RhoB promoter activity by the p38 inhibitor and knockdown of c-Jun using siRNA occurred through the distal CCAAT box. Immunoprecipitation and DNA affinity protein binding assays revealed the association of c-Jun and p300 via NF-YA and the dissociation of histone deacetylase 1 (HDAC1) via c-Jun recruitment to the CCAAT boxes of the RhoB promoter. These results suggest that the activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins to the distal CCAAT box of the RhoB promoter in Jurkat cells.
authors.affiliation: Genome Research Center, KRIBB, Daejeon 305-806, Republic of Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Ahn
authors.forename: Jeong-Hae
authors.initials: JH
authors.lastname: Choi
authors.forename: Misun
authors.initials: M
authors.lastname: Won
authors.forename: Chang-Mo
authors.initials: CM
authors.lastname: Kang
authors.forename: Mi-Rang
authors.initials: MR
authors.lastname: Gyun
authors.forename: Hee-Moon
authors.initials: HM
authors.lastname: Park
authors.forename: Chun-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Kyung-Sook
authors.initials: KS
authors.lastname: Chung
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D023081:CCAAT-Binding Factor / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000528:radiation effects*; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000235:genetics*
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D023081:CCAAT-Binding Factor; C492061:NFYA protein, human; D016755:Proto-Oncogene Proteins c-jun; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D020743:rhoB GTP-Binding Protein