title: dp5/HRK is a c-Jun target gene and required for apoptosis induced by potassium deprivation in cerebellar granule neurons.
abstract: In cerebellar granule neurons, a BH3-only Bcl-2 family member, death protein 5/harakiri, is up-regulated in a JNK-dependent manner during apoptosis induced by potassium deprivation. However, it is not clear whether c-Jun is directly involved in the induction of dp5. Here, we showed that the up-regulation of dp5, but not fas ligand and bim, after potassium deprivation was suppressed by the expression of a dominant negative form of c-Jun. Deletion analysis of the 5'-flanking sequence of the dp5 gene revealed that a major responsive element responsible for the induction by potassium deprivation is an ATF binding site located at -116 to -109 relative to the transcriptional start site. Mutation of this site completely abolished promoter activation. Furthermore, a gel shift assay showed that a specific complex containing c-Jun and ATF2 recognized this site and increased in potassium-deprived cerebellar granule neurons. Chromatin immunoprecipitation demonstrated that c-Jun was able to bind to this site in vivo. Finally, we demonstrated that knockdown of Dp5 by small interfering RNA rescued neurons from potassium deprivation-induced apoptosis. Taken together, these results suggest that dp5 is a target gene of c-Jun and plays a critical role in potassium deprivation-induced apoptosis in cerebellar granule neurons.
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.forename: Chunyi
authors.initials: C
authors.lastname: Ying
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Yuan
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liu
authors.forename: Bingquan
authors.initials: B
authors.lastname: Lai
authors.forename: Wenming
authors.initials: W
authors.lastname: Li
authors.forename: Ruzhu
authors.initials: R
authors.lastname: Chen
authors.forename: Yick-Pang
authors.initials: YP
authors.lastname: Ching
authors.forename: Mingtao
authors.initials: M
authors.lastname: Li
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005799:Genes, Dominant / Q000502:physiology; D016758:Genes, jun / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D011188:Potassium / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000502:physiology; D017384:Sequence Deletion; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D051698:Activating Transcription Factor 2; D051017:Apoptosis Regulatory Proteins; C497107:Atf2 protein, rat; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D053222:Fas Ligand Protein; C484585:Hrk protein, rat; D008565:Membrane Proteins; D009479:Neuropeptides; D011518:Proto-Oncogene Proteins; D011188:Potassium