RGD Reference Report - Down-regulation Cdc42 attenuates neuronal apoptosis through inhibiting MLK3/JNK3 cascade during ischemic reperfusion in rat hippocampus. - Rat Genome Database

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Down-regulation Cdc42 attenuates neuronal apoptosis through inhibiting MLK3/JNK3 cascade during ischemic reperfusion in rat hippocampus.

Authors: Zhao, J  Pei, DS  Zhang, QG  Zhang, GY 
Citation: Zhao J, etal., Cell Signal. 2007 Apr;19(4):831-43. Epub 2006 Dec 8.
RGD ID: 2298583
Pubmed: PMID:17161586   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cellsig.2006.10.006   (Journal Full-text)

JNK signaling pathway is activated and involved in the selective neuronal death in the hippocampal CA1 subfield following cerebral ischemia. However, little is known about upstream partner controlling the pathway. Here we reported that ischemia/reperfusion significantly elevated Cdc42 activity, enhanced assembly of the Cdc42-MLK3 complex and activation of JNK pathway. Most importantly, knock-down endogenous Cdc42 selectively suppressed the MLK3/MKK7/JNK3 cascade, and subsequently blocked the phosphorylation of c-Jun and FasL expression. Meanwhile, Bcl-2 was inactivated and the release of cytochrome c was diminished. These alterations eventually perturbed the caspase-3 activation as well as post-ischemic neuronal cell death. Taken together, our findings strongly suggest that Cdc42 serves as an upstream activator and modulates JNK-mediated apoptosis machinery in vivo, which ultimately results in neuronal apoptosis via nuclear and non-nuclear pathways. Thus, Cdc42 may be a potential therapeutic target in ischemic brain injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Reperfusion Injury  ISOCdc42 (Rattus norvegicus)2298583; 2298583protein:increased activation:hippocampus CA1RGD 
Reperfusion Injury  IDA 2298583protein:increased activation:hippocampus CA1RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of JNK cascade  IDA 2298583 RGD 
positive regulation of neuron apoptotic process  IMP 2298583 RGD 
protein autophosphorylation  IDA 2298583 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Cdc42  (cell division cycle 42)
Map3k11  (mitogen-activated protein kinase kinase kinase 11)

Genes (Mus musculus)
Cdc42  (cell division cycle 42)

Genes (Homo sapiens)
CDC42  (cell division cycle 42)


Additional Information