Requirement of clathrin heavy chain for p53-mediated transcription
Requirement of clathrin heavy chain for p53-mediated transcription
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DOI：
10.1101/gad.1381906
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发表时间：
2006-05-01
影响因子：
10.5
通讯作者：
Taya, Y
中科院分区：
文献类型：
--
作者：
Enari, M;Ohmori, K;Taya, Y
p53蛋白是一种转录因子，其激活各种基因，这些基因负责响应DNA损伤而生长停滞和/或凋亡。在这里，我们报告，网格蛋白重链（CHC）结合p53，并有助于p53介导的转录。已知CHC是作为囊泡转运蛋白发挥功能的胞质蛋白。然而，我们发现，CHC不仅存在于细胞质中，而且在细胞核中。CHC表达增强p53依赖的反式激活，而RNA干扰（RNAi）减少CHC表达减弱其转录活性。此外，CHC在体内结合p53应答启动子并稳定p53-p300相互作用以促进p53介导的转录。因此，核CHC是p53靶基因的反式激活所必需的，并且起着与网格蛋白介导的内吞作用不同的作用。
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 transctiption. Thus, nuclear CHC is required for the transactivation of p53 target genes and plays a distinct role from clathrin-mediated endocytosis.