Journal
EPIGENETICS
Volume 2, Issue 2, Pages 92-99Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/epi.2.2.4326
Keywords
transcriptional coactivator; the 26S proteasome; ubiquitin; aggresome; histone deacetylase inhibitor
Ask authors/readers for more resources
The protein level of transcriptional coactivator p300, an essential nuclear protein, is critical to a broad array of cellular activities including embryonic development, cell differentiation and proliferation. We have previously established that histone deacetylase inhibitor such as valproic acid induces p300 degradation through the 26S proteasome pathway. Here, we report the roles of cellular trafficking and spatial redistribution in valproic acid-induced p300 turnover. Our study demonstrates that p300 is redistributed to the cytoplasm prior to valproic acid-induced turnover. Inhibition of proteasome-dependent protein degradation, does not prevent nucleo-cytoplasmic shuttling of p300, rather sequesters the cytoplasmic p300 to a distinct perinuclear region. In addition, the formation of p300 aggregates in the perinuclear region depends on functional micro tubule networks and correlates with p300 ubiquitination. Our work establishes, for the first time, that p300 is also a substrate of the cytoplasmic ubiquitin-proteasome system and provides insight on how cellular trafficking and spatial redistribution regulate the availability and activity of transcriptional coactivator p300.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available