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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2007-10-15
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30901-9
pubmed:meshHeading
pubmed-meshheading:17428807-Activating Transcription Factor 2, pubmed-meshheading:17428807-Animals, pubmed-meshheading:17428807-Apoptosis, pubmed-meshheading:17428807-Apoptosis Regulatory Proteins, pubmed-meshheading:17428807-Base Sequence, pubmed-meshheading:17428807-Cells, Cultured, pubmed-meshheading:17428807-Cerebellum, pubmed-meshheading:17428807-Cytoplasmic Granules, pubmed-meshheading:17428807-Fas Ligand Protein, pubmed-meshheading:17428807-Genes, Dominant, pubmed-meshheading:17428807-Genes, jun, pubmed-meshheading:17428807-Membrane Proteins, pubmed-meshheading:17428807-Neurons, pubmed-meshheading:17428807-Neuropeptides, pubmed-meshheading:17428807-Potassium, pubmed-meshheading:17428807-Proto-Oncogene Proteins, pubmed-meshheading:17428807-Rats, pubmed-meshheading:17428807-Rats, Sprague-Dawley, pubmed-meshheading:17428807-Response Elements, pubmed-meshheading:17428807-Sequence Deletion, pubmed-meshheading:17428807-Transcription, Genetic, pubmed-meshheading:17428807-Up-Regulation
pubmed:year
2007
pubmed:articleTitle
dp5/HRK is a c-Jun target gene and required for apoptosis induced by potassium deprivation in cerebellar granule neurons.
pubmed:affiliation
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't