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PMID:20496123

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Citation

Hwang, S, Kim, D, Choi, G, An, SW, Hong, YK, Suh, YS, Lee, MJ and Cho, KS (2010) Parkin suppresses c-Jun N-terminal kinase-induced cell death via transcriptional regulation in Drosophila. Mol. Cells 29:575-80

Abstract

Parkin is the most prevalent genetic factor in the onset of autosomal recessive juvenile parkinsonism (AR-JP), and mutations in parkin has been reported to cause motor defects, which result from dopamine deficiency caused by dopaminergic neuronal cell death. Activation of c-Jun N-terminal kinase (JNK) has also been implicated in neuronal cell death in Parkinson's disease (PD). Moreover, Drosophila models for AR-JP, loss of function mutants of Drosophila parkin, also show dopaminergic neural degeneration associated with hyperactivation of JNK, increased apoptosis, and mitochondrial defects. However, the molecular mechanism by which Parkin protects cells from apoptosis remains unclear. In the present study, we tested whether Drosophila Parkin suppressed the JNK signaling pathway in developing tissues. Ectopically expressed parkin strongly suppressed the constitutively active form of Hemipterous (Hep(CA)), a Drosophila JNK kinase that induces an eye degeneration phenotype and apoptosis in the eye imaginal disc. Moreover, parkin also suppressed extra vein formation induced by Basket (Bsk), a Drosophila JNK. Interestingly, the bsk mRNA level was markedly reduced by parkin over-expression, suggesting that the effect of parkin on the phenotype induced by activation of JNK signaling was achieved by transcriptional regulation. Furthermore, we found that the expression level of JNK target genes was reduced by parkin over-expression. Taken together, these results suggest that Drosophila Parkin suppresses JNK signaling by reducing bsk transcription.

Links

PubMed Online version:10.1007/s10059-010-0068-1

Keywords

Animals; Apoptosis/genetics; Disease Models, Animal; Drosophila; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Eye/blood supply; Eye/embryology; Eye/growth & development; Gene Expression Regulation, Developmental/genetics; Humans; Mitogen-Activated Protein Kinase Kinases/genetics; Mitogen-Activated Protein Kinase Kinases/metabolism; Mutation/genetics; Neovascularization, Physiologic/genetics; Neurons/metabolism; Neurons/pathology; Parkinsonian Disorders/genetics; Parkinsonian Disorders/metabolism; Receptor, EphA5/biosynthesis; Receptor, EphA5/genetics; Signal Transduction/genetics; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:PRKN

involved_in

GO:0046329: negative regulation of JNK cascade

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0010303

P

Seeded From UniProt

complete

DROME:PRKN

involved_in

GO:0046329: negative regulation of JNK cascade

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0000229

P

Seeded From UniProt

complete

DROME:Q7KTX7

involved_in

GO:0046329: negative regulation of JNK cascade

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0010303

P

Seeded From UniProt

complete

DROME:Q7KTX7

involved_in

GO:0046329: negative regulation of JNK cascade

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0000229

P

Seeded From UniProt

complete

Notes

See also

References

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