RRC ID 5573
著者 Weidenfeld-Baranboim K, Hasin T, Darlyuk I, Heinrich R, Elhanani O, Pan J, Yokoyama KK, Aronheim A.
タイトル The ubiquitously expressed bZIP inhibitor, JDP2, suppresses the transcription of its homologue immediate early gene counterpart, ATF3.
ジャーナル Nucleic Acids Res
Abstract JDP2 is a ubiquitously expressed bZIP repressor protein. JDP2 binds TPA response element and cyclic AMP response element located within various promoters. JDP2 displays a high degree of homology to the immediate early gene ATF3. ATF3 plays a crucial role in the cellular adaptive response to multiple stress insults as well as growth stimuli. We have identified ATF3 as a potential target gene for JDP2 repression. JDP2 regulates the ATF3 promoter potentially through binding to both the consensus ATF/CRE site and a non-consensus ATF3 auto-repression DNA-binding element. Expression of ATF3 protein in wild-type mouse embryo fibroblast (MEF) cells is below the detectable levels, whereas, JDP2 disrupted MEF cells display noticeable level of ATF3 protein. Following either serum or ER stress stimulation, ATF3 expression is potentiated in JDP2-KO fibroblast cells as compared with wild-type cells. Mice with either JDP2 over-expression or JDP2 disruption display undetectable level of ATF3 protein. However, ATF3 induction in response to either growth or stress signals is dependent on JDP2 expression level. ATF3 induction is attenuated in JDP2 over-expressing mice whereas is potentiated in JDP2-KO mice as compared with the corresponding wild-type mice. Collectively, the data presented strongly suggest that JDP2 plays a role in the determination of the ATF3 adaptive cellular threshold response to different stress insults and growth stimuli.
巻・号 37(7)
ページ 2194-203
公開日 2009-4-1
DOI 10.1093/nar/gkp083
PII gkp083
PMID 19233874
PMC PMC2673429
MeSH Activating Transcription Factor 3 / genetics* Activating Transcription Factor 3 / metabolism Angiotensin II / pharmacology Animals Binding Sites Cell Line Gene Expression Regulation* Heart / drug effects Humans Isoproterenol / pharmacology Liver / drug effects Liver / metabolism Mice Mice, Knockout Mice, Transgenic Myocardium / metabolism Promoter Regions, Genetic Repressor Proteins / genetics Repressor Proteins / metabolism* Transcription, Genetic
IF 11.502
引用数 33
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
実験動物マウス RBRC00861