Recommend Epigenetics to your librarian today. Download form here.
Sign up for Table of Contents Alerts.
The official journal of the Epigenetics Society.
Email this page
Print this page
Research Paper
Ubiquitin-Dependent Distribution of the Transcriptional Coactivator p300 in Cytoplasmic Inclusion Bodies
Jihong Chen, Sabina Halappanavar, John Th’ng and Qiao Li
volume 2 | issue 2
april/may/june 2007Pages: 92 - 99
This is an open-access article
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
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 microtubule 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
Jihong Chen
University of Ottawa; Ottawa, Ontario, Canada
Sabina Halappanavar
University of Ottawa; Ottawa, Ontario, Canada
John Th’ng
University of Ottawa; Ottawa, Ontario, Canada
Qiao Li
University of Ottawa; Ottawa, Ontario, Canada
This is an open-access article
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.