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  • Original Paper
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PCAF is a coactivator for p73-mediated transactivation

Abstract

The tumor suppressor p53-related p73 shares significant amino-acid sequence identity with p53. Like p53, p73 recognizes canonical p53 DNA-binding sites and activates p53-responsive target genes and induces apoptosis. Moreover, transcription coactivator p300/CBP binds to and coactivates with both p53 and p73 in stimulating the expression of their target genes. Here, we report that coactivator PCAF binds to p73. The N-terminal transactivation domain (TAD) and the conserved oligomerization domain (OD) of p73 are both required for its interaction with PCAF. Conversely, PCAF's HAT-domain is required for and both the N-terminal region and Bromo domain enhance binding of PCAF to p73. Significantly, PCAF stimulates p73-mediated transactivation, and binding of PCAF to p73 is necessary for p73's transactivation activity. PCAF-specific siRNA dramatically reduces p73-mediated transactivation. Stimulation of p73-mediated transactivation by PCAF requires the HAT domain of PCAF and the p53-binding site within the p21 promoter. In vivo, coexpression of wild-type, but not HAT-deficient PCAF with p73β markedly increases p21 expression. Furthermore, cotransfection of PCAF and p73 leads to increased apoptosis and reduced colony formation. Collectively, these data suggest that p73 recruit PCAF to specific promoters to activate the transcription of p73 target genes.

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Acknowledgements

We thank B Vogelstein, M Kaghad and H Arakawa for generously providing plasmids. We also thank Frederique Fricsh for technical assistance.

This work was supported by National Institutes of Health grant R01 CA92236 (DL), and in part by Canadian Institutes of Health Research grants MOP-14109 and MOP-42429 (DL) and National Cancer Institute of Canada grants (XJY). In addition, D Liao received pilot project grants from Biomedical Research Support Program for Medical Schools awarded to the University of Florida College of Medicine by Howard Hughes Medical Institute.

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Correspondence to Daiqing Liao.

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Zhao, L., Liu, Y., Bertos, N. et al. PCAF is a coactivator for p73-mediated transactivation. Oncogene 22, 8316–8329 (2003). https://doi.org/10.1038/sj.onc.1206916

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