RGD Reference Report - Neuroprotection by histone deacetylase-7 (HDAC7) occurs by inhibition of c-jun expression through a deacetylase-independent mechanism. - Rat Genome Database

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Neuroprotection by histone deacetylase-7 (HDAC7) occurs by inhibition of c-jun expression through a deacetylase-independent mechanism.

Authors: Ma, C  D'Mello, SR 
Citation: Ma C and D'Mello SR, J Biol Chem. 2011 Feb 11;286(6):4819-28. doi: 10.1074/jbc.M110.146860. Epub 2010 Nov 30.
RGD ID: 9681718
Pubmed: PMID:21118817   (View Abstract at PubMed)
PMCID: PMC3039335   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M110.146860   (Journal Full-text)

Histone deacetylase (HDAC) 7 is a member of the HDAC family of deacetylases. Although some of the HDAC proteins have been shown to regulate neuronal survival and death, whether HDAC7 has a similar role is not known. In this study, we show that HDAC7 protects neurons from apoptosis. In cerebellar granule neurons (CGNs) primed to undergo apoptosis by low potassium treatment, expression of HDAC7 protein is reduced. Reduced expression is also observed in CGNs induced to die by pharmacological inhibition of the proteasome, in cortical neurons treated with homocysteic acid, and in the striatum of R6/2 transgenic mice, a commonly used genetic model of Huntington disease. Forced expression of HDAC7 in cultured CGNs blocks low potassium-induced death, and shRNA-mediated suppression of its expression induces death in otherwise healthy neurons. HDAC7-mediated neuroprotection does not require its catalytic domain and cannot be inhibited by chemical inhibitors of HDACs. Moreover, pharmacological inhibitors of the PI3K-Akt or Raf-MEK-ERK signaling pathways or that of PKA, PKC, and Ca(2+)/calmodulin-dependent protein kinase fail to reduce neuroprotection by HDAC7. We show that stimulation of c-jun expression, an essential feature of neuronal death, is prevented by HDAC7. shRNA-mediated suppression of HDAC7 expression leads to an increase in c-jun expression. Inhibition of c-jun expression by HDAC7 is mediated at the transcriptional level by its direct association with the c-jun gene promoter. Taken together, our results indicate that HDAC7 is a neuroprotective protein acting by a mechanism that is independent of its deacetylase activity but involving the inhibition of c-jun expression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Huntington's disease  ISOHdac7 (Mus musculus)9681718; 9681718protein:decreased expression:brain:RGD 
Huntington's disease  IEP 9681718protein:decreased expression:brain:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neuron apoptotic process  IEP 9681718 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdac7  (histone deacetylase 7)

Genes (Mus musculus)
Hdac7  (histone deacetylase 7)

Genes (Homo sapiens)
HDAC7  (histone deacetylase 7)


Additional Information