RGD Reference Report - POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis. - Rat Genome Database

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POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis.

Authors: Xu, Z  Kukekov, NV  Greene, LA 
Citation: Xu Z, etal., EMBO J. 2003 Jan 15;22(2):252-61.
RGD ID: 2293340
Pubmed: PMID:12514131   (View Abstract at PubMed)
PMCID: PMC140096   (View Article at PubMed Central)
DOI: DOI:10.1093/emboj/cdg021   (Journal Full-text)

We report that the multidomain protein POSH (plenty of SH3s) acts as a scaffold for the JNK pathway of neuronal death. This pathway consists of a sequential cascade involving activated Rac1/Cdc42, mixed-lineage kinases (MLKs), MAP kinase kinases (MKKs) 4 and 7, c-Jun N-terminal kinases (JNKs) and c-Jun, and is required for neuronal death induced by various means including nerve growth factor (NGF) deprivation. In addition to binding GTP-Rac1 as described previously, we find that POSH binds MLKs both in vivo and in vitro, and complexes with MKKs 4 and 7 and with JNKs. POSH overexpression promotes apoptotic neuronal death and this is suppressed by dominant-negative forms of MLKs, MKK4/7 and c-Jun, and by an MLK inhibitor. Moreover, a POSH antisense oligonucleotide and a POSH small interfering RNA (siRNA) suppress c-Jun phosphorylation and neuronal apoptosis induced by NGF withdrawal. Thus, POSH appears to function as a scaffold in a multiprotein complex that links activated Rac1 and downstream elements of the JNK apoptotic cascade.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
JunRatpositive regulation of neuron apoptotic process  IMP  RGD 
Map2k4Ratpositive regulation of neuron apoptotic process  IMP  RGD 
Map2k7Ratpositive regulation of neuron apoptotic process  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Jun  (Jun proto-oncogene, AP-1 transcription factor subunit)
Map2k4  (mitogen activated protein kinase kinase 4)
Map2k7  (mitogen activated protein kinase kinase 7)


Additional Information