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Characterization of p73 functional domains necessary for transactivation and growth suppression

Oncogene volume 22, pages 4333–4347 (2003)Cite this article

Abstract

p73, a p53 family member, is highly similar to p53 in both structure and function. Like p53, the p73 protein contains an N-terminal activation domain, a DNA-binding domain, a tetramerization domain, and several PXXP motifs. Previously, we and others have shown that some functional domains in p53, such as the DNA-binding and tetramerization domains, are required for inducing both cell cycle arrest and apoptosis whereas others, such as the second activation domain, the proline-rich domain, and the C-terminal basic domain, are only required for inducing apoptosis. To determine the activity of p73 functional domains, we have generated stable inducible cell lines that express p73β and various mutants deficient in one or more functional domains. We found that in addition to the DNA-binding domain, p73-mediated growth suppression requires the N-terminal activation domain and the tetramerization domain. However, unlike p53, p73-mediated apoptosis does not require the region adjacent to the activation domain or the entire C-terminal region. Interestingly, while the N- or the C-terminal PXXP motifs are dispensable for p73 function, deletion of both the N- and the C-terminal PXXP motifs renders p73 inactive in transactivation. In addition, we found that substitution of two conserved tandem hydrophobic residues with two hydrophilic ones, which can abrogate the activity of the first activation domain in p53, has no effect on p73 transcriptional activity. Together, we showed that the p73 protein has its own unique determinants for transactivation and growth suppression.

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Acknowledgements

We thank Ebbie Shafizadeh for cloning human p73β, Steve Anander and Rob Fang for generating some p73 mutant constructs, and Yiman Zheng for technical assistance. This work is supported in part by NIH Grant CA 81237.

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  1. Yijun Wu

    Present address: Institute of Zoology, Chinese Academy of Science, Beijing, China

Authors and Affiliations

  1. Department of Cell Biology, The University of Alabama at Birmingham, Birmingham, ALA 35294-0005, USA

    Susan Nozell, Yijun Wu, Kelly McNaughton, Gang Liu, Amy Willis, Jason C Paik & Xinbin Chen

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Correspondence to Xinbin Chen.

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Nozell, S., Wu, Y., McNaughton, K. et al. Characterization of p73 functional domains necessary for transactivation and growth suppression. Oncogene 22, 4333–4347 (2003). https://doi.org/10.1038/sj.onc.1206470

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