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Koike, M., Fukushi, J., Ichinohe, Y., Higashimae, N., Fujishiro, M., Sasaki, C., Yamaguchi, M., Uchihara, T., Yagishita, S., Ohizumi, H., Hori, S., Kakizuka, A. (2010). Valosin-containing Protein (VCP) in Novel Feedback Machinery between Abnormal Protein Accumulation and Transcriptional Suppression.  J. Biol. Chem. 285(28): 21736--21749.
FlyBase ID
FBrf0211185
Publication Type
Research paper
Abstract

Abnormal protein accumulation is often observed in human neurodegenerative disorders such as polyglutamine diseases and Parkinson disease. Genetic and biochemical analyses indicate that valosin-containing protein (VCP) is a crucial molecule in the pathogenesis of human neurodegenerative disorders. We report here that VCP was specifically modified in neuronal cells with abnormal protein accumulation; this modification caused the translocation of VCP into the nucleus. Modification-mimic forms of VCP induced transcriptional suppression with deacetylation of core histones, leading to cell atrophy and the decrease of de novo protein synthesis. Preventing VCP nuclear translocation in polyglutamine-expressing neuronal cells and Drosophila eyes mitigated neurite retraction and eye degenerations, respectively, concomitant with the recovery of core histone acetylation. This represents a novel feedback mechanism that regulates abnormal protein levels in the cytoplasm during physiological processes, as well as in pathological conditions such as abnormal protein accumulation in neurodegenerations.

PubMed ID
PubMed Central ID
PMC2898386 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Biol. Chem.
    Title
    Journal of Biological Chemistry
    Publication Year
    1905-
    ISBN/ISSN
    0021-9258
    Data From Reference
    Alleles (3)
    Genes (5)
    Human Disease Models (1)
    Cell Lines (1)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (3)