Regulation of transcriptional coactivator p300 by posttranslational modification

通过翻译后修饰调节转录辅激活因子 p300

• 批准号: RGPIN-2017-03734
• 负责人: Li, Qiao
• 金额: $ 2.91万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629910
• 关键词: Regulation; transcriptional; coactivator; p300; posttranslational

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.

转录辅激活因子p300具有内在的组蛋白乙酰转移酶（HAT）活性，并且对于许多细胞过程是重要的。 因此，对p300的严格控制对于确保基因座特异性组蛋白乙酰化和基因调控至关重要。 我们以前已经建立了p300是动态调节的翻译后修饰和不同的细胞分布。 我们是第一个表明，p300是由细胞质蛋白酶体系统调制。 此外，我们已经确定Akt/蛋白激酶B是p300的正调节因子，而蛋白磷酸酶2A（PP 2A）的B56γ3调节亚基是负调节因子。 我们的工作提供了新的见解，细胞运输和空间再分布控制蛋白质的稳定性和转录活性的p300。 最近，我们发现，p300的调控在一个谱系特异性的方式在肌分化。 因此，我们打算利用我们的研究结果来确定与成肌细胞分化相关的谱系特异性p300调控的分子机制。