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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Requirement of clathrin heavy chain for p53-mediated transcription
Masato Enari1, Kazuji Ohmori, Issay Kitabayashi
1Radiobiology Division, Chuo-ku, Tokyo 104-0045, Japan.
Abstract:
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.
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