Regulation of transcriptional coactivator p300 by posttranslational modification

点击翻译按钮获取中文摘要

The transcriptional coactivator p300 possess an intrinsic histone acetyltransferase (HAT) activity and is important for many cellular processes. A tight control of p300 is therefore critical to ensure locus-specific histone acetylation and gene regulation. We have established previously that p300 is dynamically regulated by posttranslational modification and distinct cellular distribution. We are the first to show that p300 is modulated by the cytoplasmic proteasome system. In addition, we have established that Akt/protein kinase B is a positive regulator of p300, while the B56γ3 regulatory subunit of protein phosphatase 2A (PP2A) is a negative regulator. Our works have provided novel insights into how cellular trafficking and spatial redistribution control the protein stability and transcriptional activity of p300. Recently, we found that p300 is regulated in a lineage specific manner during myogenic differentiation. As such, we intend to leverage our findings to define the molecular mechanisms underlying lineage-specific p300 regulation associated with myoblast differentiation.