Collapsin response mediator protein 3 deacetylates histone H4 to mediate nuclear condensation and neuronal death

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DOIResolve DOI: http://doi.org/10.1038/srep01350
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TypeArticle
Journal titleScientific Reports
ISSN2045-2322
Volume3
Article number1350
SubjectDpysl4 protein, mouse; glutamic acid; histone; histone deacetylase; nerve protein; transcription factor E2F1; tubulin; acetylation; animal; article; cell death; cell line; cell nucleus; drug effect; female; gene expression regulation; gene silencing; genetics; human; metabolism; mouse; nerve cell; protein binding; protein transport; ultrastructure; Acetylation; Animals; Cell Death; Cell Line; Cell Nucleus; E2F1 Transcription Factor; Female; Gene Expression Regulation; Gene Knockdown Techniques; Glutamic Acid; Histone Deacetylases; Histones; Humans; Mice; Nerve Tissue Proteins; Neurons; Protein Binding; Protein Transport; Tubulin
AbstractCRMP proteins play critical regulatory roles during semaphorin-mediated neurite outgrowth, neuronal differentiation and death. Albeit having a high degree of structure and sequence resemblance to that of liver dihydropyrimidinase, purified rodent brain CRMPs do not hydrolyze dihydropyrimidinase substrates. Here we found that mouse CRMP3 has robust histone H4 deacetylase activity. During excitotoxicity-induced mouse neuronal death, calpain-cleaved, N-terminally truncated CRMP3 undergoes nuclear translocation to cause nuclear condensation through deacetylation of histone H4. CRMP3-mediated deacetylation of H4 leads to de-repression of the E2F1 gene transcription and E2F1-dependent neuronal death. These studies revealed a novel mechanism of CRMP3 in neuronal death. Together with previous well established bodies of literature that inhibition of histone deacetylase activity provides neuroprotection, we envisage that inhibition of CRMP3 may represent a novel therapeutic approach towards excitotoxicity-induced neuronal death.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Human Health Therapeutics (HHT-TSH)
Peer reviewedYes
NPARC number21269893
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Record identifier8310cefe-ddef-4f25-97e6-cd6dab878a39
Record created2013-12-13
Record modified2016-05-09
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