B56 Regulatory Subunit of Protein Phosphatase 2A Mediates Valproic Acid-Induced p300 Degradation
| Autor: | Qiao Li, Jonathan R. St-Germain, Jihong Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Proteasome Endopeptidase Complex
medicine.drug_class Protein subunit DUSP6 Gene Expression Coactivator Okadaic Acid medicine Phosphoprotein Phosphatases Humans Protein Phosphatase 2 Nuclear protein Enzyme Inhibitors RNA Small Interfering Molecular Biology Regulation of gene expression biology Valproic Acid Histone deacetylase inhibitor Nuclear Proteins Cell Biology Protein phosphatase 2 Protein Subunits Biochemistry Gene Expression Regulation GATAD2B biology.protein Trans-Activators HeLa Cells |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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