p53 directly regulates the glycosidase FUCA1 to promote chemotherapy-induced cell death

Baudot, A. D., Crighton, D., O'Prey, J., Somers, J., Sierra Gonzalez, P. and Ryan, K. M. (2016) p53 directly regulates the glycosidase FUCA1 to promote chemotherapy-induced cell death. Cell Cycle, 15(17), pp. 2299-2308. (doi:10.1080/15384101.2016.1191714) (PMID:27315169) (PMCID:PMC5004703)

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Abstract

p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. We show that p53 transcriptionally activates FUCA1 and that p53 modulates fucosidase activity via FUCA1 up-regulation. Importantly, we also report that chemotherapeutic drugs induce FUCA1 and fucosidase activity in a p53-dependent manner. In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy.

Item Type:Articles
Additional Information:This work was supported by Worldwide Cancer Research and Cancer Research UK.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:O'Prey, Mr James and Crighton, Dr Diane and Somers, Miss Joanna and Baudot, Dr Alice and Sierra Gonzalez, Pablo and Ryan, Professor Kevin
Authors: Baudot, A. D., Crighton, D., O'Prey, J., Somers, J., Sierra Gonzalez, P., and Ryan, K. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Cycle
Publisher:Taylor & Francis
ISSN:1538-4101
ISSN (Online):1551-4005
Published Online:17 June 2016
Copyright Holders:Copyright © 2016 Alice D. Baudot, Diane Crighton, Jim O’Prey, Joanna Somers, Pablo Sierra Gonzalez, and Kevin M. Ryan
First Published:First published in Cell Cycle 15(17): 2299-2308
Publisher Policy:Reproduced under a Creative Commons License

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