Requirement of clathrin heavy chain for p53-mediated transcription

  1. Masato Enari1,2,4,
  2. Kazuji Ohmori1,2,4,
  3. Issay Kitabayashi3, and
  4. Yoichi Taya1,2,5
  1. 1 Radiobiology Division,
  2. 2 Solution-Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST),
  3. 3 Molecular Oncology Division at the National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan
  1. 4

    ↵4 These authors contributed equally to this work.

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 transctiption. 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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  1. Published in Advance April 17, 2006, doi: 10.1101/gad.1381906 Genes & Dev. 20: 1087-1099 Copyright © 2006, Cold Spring Harbor Laboratory Press

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