RGD Reference Report - dp5/HRK is a c-Jun target gene and required for apoptosis induced by potassium deprivation in cerebellar granule neurons. - Rat Genome Database

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dp5/HRK is a c-Jun target gene and required for apoptosis induced by potassium deprivation in cerebellar granule neurons.

Authors: Ma, C  Ying, C  Yuan, Z  Song, B  Li, D  Liu, Y  Lai, B  Li, W  Chen, R  Ching, YP  Li, M 
Citation: Ma C, etal., J Biol Chem. 2007 Oct 19;282(42):30901-9. Epub 2007 Apr 11.
RGD ID: 2290488
Pubmed: PMID:17428807   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M608694200   (Journal Full-text)

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.



Gene Ontology Annotations    

Molecular Function

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Atf2  (activating transcription factor 2)
Hrk  (harakiri, BCL2 interacting protein)
Jun  (Jun proto-oncogene, AP-1 transcription factor subunit)

Genes (Mus musculus)
Hrk  (harakiri, BCL2 interacting protein (contains only BH3 domain))

Genes (Homo sapiens)
HRK  (harakiri, BCL2 interacting protein)


Additional Information