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Requirement of clathrin heavy chain for p53-mediated transcription.

机译:网格蛋白重链对p53介导的转录的要求。

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摘要

The p53 protein is a transcription factor that activates various genes responsible for growth arrest and/or apoptosis in response to DNA damage. Here, we report that clathrin heavy chain (CHC) binds to p53 and contributes to p53-mediated transcription. CHC is known to be a cytosolic protein that functions as a vesicle transporter. We found, however, that CHC exists not only in cytosol but also in nuclei. CHC expression enhances p53-dependent transactivation, whereas the reduction of CHC expression by RNA interference (RNAi) attenuates its transcriptional activity. Moreover, CHC binds to the p53-responsive promoter in vivo and stabilizes p53-p300 interaction to promote p53-mediated transcription. Thus, nuclear CHC is required for the transactivation of p53 target genes and plays a distinct role from clathrin-mediated endocytosis.
机译:p53蛋白是一种转录因子,可响应DNA损伤而激活负责生长停滞和/或凋亡的各种基因。在这里,我们报告网格蛋白重链(CHC)绑定到p53,并有助于p53介导的转录。众所周知,CHC是一种充当囊泡转运蛋白的胞质蛋白。但是,我们发现CHC不仅存在于细胞质中,而且还存在于细胞核中。 CHC表达增强p53依赖的反式激活,而RNA干扰(RNAi)导致CHC表达的减少会减弱其转录活性。此外,CHC在体内与p53反应性启动子结合,并稳定p53-p300相互作用以促进p53介导的转录。因此,核CHC是p53靶基因反式激活所必需的,并且与网格蛋白介导的内吞作用起着独特的作用。

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