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

我们之前已经鉴定出网格蛋白重链是一种p53结合蛋白。在本研究中，CHC存在于细胞核中，通过增强p53与组蛋白乙酰转移酶p300之间的相互作用，促进p53的反式活化。我们还发现核有丝分裂装置（NuMA）是核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，构建了CHC-p53相互作用的结构模型，并鉴定了CHC中一个对p53反活化很重要的氨基酸残基。质膜相关p53参与chc依赖性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.