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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.; Vousden, K.H.

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Authors

A.G. Trinidad

P.T. Caswell

J.C. Norman

K.H. Vousden



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.

Citation

Muller, P., Trinidad, A., Caswell, P., Norman, J., & Vousden, K. (2014). Mutant p53 regulates dicer through p63-dependent and -independent mechanisms to promote an invasive phenotype. Journal of Biological Chemistry, 289(1), 122-132. https://doi.org/10.1074/jbc.m113.502138

Journal Article Type Article
Online Publication Date Nov 12, 2013
Publication Date 2014-01
Deposit Date Oct 26, 2021
Publicly Available Date Jan 14, 2022
Journal Journal of Biological Chemistry
Print ISSN 0021-9258
Electronic ISSN 1083-351X
Publisher American Society for Biochemistry and Molecular Biology
Peer Reviewed Peer Reviewed
Volume 289
Issue 1
Pages 122-132
DOI https://doi.org/10.1074/jbc.m113.502138
Public URL https://durham-repository.worktribe.com/output/1225419

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