Study on the regulatory mechanism of p53 transactivation by clathrin heavy chain

我们先前已经发现，笼状蛋白重链是一种P53结合蛋白。在本研究中，CHC存在于细胞核中，并通过增强P53和组蛋白乙酰转移酶p300之间的相互作用来促进P53的反式激活。我们还鉴定了核有丝分裂装置(NUMA)是一种核CHC结合因子，并表明NUMA是CDK8介导的P53转录选择性的关键决定因素。此外，我们还构建了CHC-P53相互作用的结构模型，并确定了CHC中一个对P53反式激活起重要作用的氨基酸残基。质膜相关的P53参与CHC依赖的内吞作用和肌动蛋白介导的细胞运动的调节。

We have previously identified clathrin heavy chain as a p53-binding protein. In this study, CHC is present in nuclei and promotes p53 transactivation through the enhancement of the interaction between p53 and p300, histone acetyltransferase. We also identified nuclear mitotic apparatus (NuMA)as a nuclear CHC-binding factor and showed that NuMA was a critical determinant for p53-transcriptional selectivity mediated by Cdk8. Moreover, the structural model of CHC-p53 interaction was constructed and an amino acid residue in CHC, which is important for p53 transactivation, was identified. Plasma membrane-associated p53 is involved in the regulation of CHC-dependent endocytosis and actin-mediated cell motility.