Bipolar Research Today is a free monthly online journal that collates and summarizes the latest research about Bipolar, including details on bipolar disorder, symptoms, treatment, depression, medication.

B56 regulatory subunit of protein phosphatase 2A mediates valproic acid-induced p300 degradation.

Chen J, St-Germain JR, Li Q

Ottawa Health Research Institute, 725 Parkdale Ave., Ottawa, Ontario, Canada K1Y 4E9.

Transcriptional coactivator p300 is required for embryonic development and cell proliferation. Valproic acid, a histone deacetylase inhibitor, is widely used in the therapy of epilepsy and bipolar disorder. However, it has intrinsic teratogenic activity through unidentified mechanisms. We report that valproic acid stimulates proteasome-dependent p300 degradation through augmentation of gene expression of the B56gamma regulatory subunits of protein phosphatase 2A. The B56gamma3 regulatory and catalytic subunits of protein phosphatase 2A interact with p300. Overexpression of the B56gamma3 subunit leads to proteasome-mediated p300 degradation and represses p300-dependent transcriptional activation, which requires the B56gamma3 interaction domain of p300. Conversely, silencing of the B56gamma subunit expression by RNA interference increases the stability and transcriptional activity of the coactivator. Our study establishes the functional interaction between protein phosphatase 2A and p300 activity and provides direct evidence for signal-dependent control of p300 function.

Published 5 January 2005 in Mol Cell Biol, 25(2): 525-32.
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