Mutant p53 regulates dicer through p63-dependent and -independent mechanisms to promote an invasive phenotype

Muller, P. A.J., Trinidad, A. G., Caswell, P. T., Norman, J. C. and Vousden, K. H. (2014) Mutant p53 regulates dicer through p63-dependent and -independent mechanisms to promote an invasive phenotype. Journal of Biological Chemistry, 289(1), pp. 122-132. (doi:10.1074/jbc.M113.502138)

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Abstract

The control and processing of microRNAs (miRs) is critical in the regulation of all cellular responses. Previous studies have suggested that a reduction in the expression of certain miRs, or an overall decrease in miR processing through the partial depletion of Dicer, can promote enhanced metastatic potential. We show here that Dicer depletion can promote the invasive behavior of cells that is reflected in enhanced recycling and activation of the growth factor receptors Met and EGF receptor. These responses are also seen in response to the expression of tumor-derived mutant p53s, and we show that mutant p53 can down-regulate Dicer expression through both direct inhibition of the TAp63-mediated transcriptional activation of Dicer and a TAp63-independent control of Dicer protein expression. Our results delineate a clear relationship between mutant p53, TAp63, and Dicer that might contribute to the metastatic function of mutant p53 but, interestingly, also reveal TAp63-independent functions of mutant p53 in controlling Dicer activity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Norman, Professor James and Caswell, Dr Patrick and Vousden, Karen and Muller, Dr Patricia
Authors: Muller, P. A.J., Trinidad, A. G., Caswell, P. T., Norman, J. C., and Vousden, K. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Journal of Biological Chemistry 289(1):122-132
Publisher Policy:Reproduced under a Creative Commons License

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