Requirement of clathrin heavy chain for p53-mediated transcription.
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.
Enari
Masato
M
Radiobiology Division, Chuo-ku, Tokyo 104-0045, Japan.
Ohmori
Kazuji
K
Kitabayashi
Issay
I
Taya
Yoichi
Y
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D033922:Clathrin Heavy Chains / Q000235:genetics / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D033922:Clathrin Heavy Chains; D050880:p300-CBP Transcription Factors