| First Author | Koike M | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 28 | Pages | 21736-49 |
| PubMed ID | 20410307 | Mgi Jnum | J:165369 |
| Mgi Id | MGI:4837059 | Doi | 10.1074/jbc.M109.099283 |
| Citation | Koike M, et al. (2010) Valosin-containing protein (VCP) in novel feedback machinery between abnormal protein accumulation and transcriptional suppression. J Biol Chem 285(28):21736-49 |
| abstractText | 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. |
