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The proline-rich region of mouse p53 influences transactivation and apoptosis but is largely dispensable for these functions

Oncogene volume 22, pages 4517–4523 (2003)Cite this article

Abstract

The N-terminal proline-rich domain of human p53 has been shown to be important for the induction of apoptosis. However, the corresponding region in mouse and other species is not highly conserved and has been less well studied. In this paper, we have characterized mutants with deletions in this region of mouse p53. Our results demonstrate that deletions in the proline-rich domain have varying effects on function ranging from no effect to severe impairment of cell death activity, depending on precisely which residues are deleted. We also show that the mutants differ in their ability to transactivate different p53 target promoters. Although we have been able to obtain mutants selectively impaired for apoptosis, our data are not generally consistent with this region being a functional domain. The data are more consistent with the interpretation that the region influences function by altering local protein structure which may affect promoter discrimination.

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Acknowledgements

We thank Moshe Oren (Rehovot), Xin Lu (London) for reporter constructs, Roger Reddel (Sydney) for IIICF/c cells and Janice Royds for comments on the manuscript. The work was supported by the Health Research Council, the Cancer Society, the Royal Society and Lottery Health.

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  1. Department of Pathology, Dunedin School of Medicine, University of Otago, Box 913, Dunedin, New Zealand

    Sara J Edwards, Lynne Hananeia, Michael R Eccles, You Fang Zhang & Antony W Braithwaite

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  1. Sara J Edwards
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  2. Lynne Hananeia
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  3. Michael R Eccles
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  4. You Fang Zhang
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Correspondence to Sara J Edwards.

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Edwards, S., Hananeia, L., Eccles, M. et al. The proline-rich region of mouse p53 influences transactivation and apoptosis but is largely dispensable for these functions. Oncogene 22, 4517–4523 (2003). https://doi.org/10.1038/sj.onc.1206726

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