p53 directly regulates the glycosidase FUCA1 to promote chemotherapy-induced cell death
Open accessAbstract
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.
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The carbohydrate fucose is degraded through a fucosidase that is encoded by the p53 target FUCA1.
“The carbohydrate fucose is degraded through a fucosidase that is encoded by the p53 target FUCA1.196”
From Census and evaluation of p53 target genes (2017) · cites this paper as [196]
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Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971 · see citing works
- Authors
- Baudot, A. D., Crighton, D., O'Prey, J., Somers, J., Sierra Gonzalez, P., & Ryan, K. M.
- Affiliations
- Cancer Research UK Scotland Institute (GB)
- Cancer Research UK Beatson Institute, Garscube Estate, Glasgow, Scotland, UK
- Corresponding author
- Ryan, Kevin M.
- ORCID
- Ryan, Kevin M.
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2016-08-03
- Volume
- 15
- Issue
- 17
- Pages
- 2299-2308
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC5004703
- OpenAlex
- W2434524091
- Cited by
- 31
- References
- 49
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 8 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 1
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Cycle (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Funders
- Cancer Research UK (22903, 15816)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53, FUCA1, fucosidase, N-glycosylation, chemotherapy-induced apoptosis, transcriptional activation, programmed cell death, tumor suppression
- MeSH terms
- Antineoplastic Agents, DNA Damage, alpha-L-Fucosidase, Humans, Tumor Suppressor Protein p53, Cell Death, Cell Line, Tumor
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