The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
The p53 Tumor Suppressor in the Control of Metabolism and Ferroptosis
Open accessAbstract
The p53 tumor suppressor continues to be distinguished as the most frequently mutated gene in human cancer. It is widely believed that the ability of p53 to induce senescence and programmed cell death underlies the tumor suppressor functions of p53. However, p53 has a number of other functions that recent data strongly implicate in tumor suppression, particularly with regard to the control of metabolism and ferroptosis (iron- and lipid-peroxide-mediated cell death) by p53. As reviewed here, the roles of p53 in the control of metabolism and ferroptosis are complex. Wild-type (WT) p53 negatively regulates lipid synthesis and glycolysis in normal and tumor cells, and positively regulates oxidative phosphorylation and lipid catabolism. Mutant p53 in tumor cells does the converse, positively regulating lipid synthesis and glycolysis. The role of p53 in ferroptosis is even more complex: in normal tissues, WT p53 appears to positively regulate ferroptosis, and this pathway appears to play a role in the ability of basal, unstressed p53 to suppress tumor initiation and development. In tumors, other regulators of ferroptosis supersede p53's role, and WT p53 appears to play a limited role; instead, mutant p53 sensitizes tumor cells to ferroptosis. By clearly elucidating the roles of WT and mutant p53 in metabolism and ferroptosis, and establishing these roles in tumor suppression, emerging research promises to yield new therapeutic avenues for cancer and metabolic diseases.
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Cites
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695
Self-citationFerroptosis as a p53-mediated activity during tumour suppression
Jiang, L., Kon, N., Li, T., Wang, S.-J., Su, T., Hibshoosh, H., Baer, R., & Gu, W. (2015) · Nature · doi:10.1038/nature14344 · Cited by 3,398
Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis
Yang, W. S., Kim, K. J., Gaschler, M. M., Patel, M., Shchepinov, M. S., & Stockwell, B. R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1603244113 · Cited by 2,329
Glutaminolysis and transferrin regulate ferroptosis
Gao, M., Monian, P., Quadri, N., Ramasamy, R., & Jiang, X. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.06.011 · Cited by 2,069
Sun, X., Ou, Z., Chen, R., Niu, X., Chen, D., Kang, R., & Tang, D. (2016) · Hepatology · doi:10.1002/hep.28251 · Cited by 2,012
p53 Regulates Mitochondrial Respiration
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Tumour-associated mutant p53 drives the Warburg effect
Zhang, C., Liu, J., Liang, Y., Wu, R., Zhao, Y., Hong, X., Lin, M., Yu, H., Liu, L., Levine, A. J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3935 · Cited by 434
Inhibiting the system xC−/glutathione axis selectively targets cancers with mutant-p53 accumulation
Liu, D. S., Duong, C. P., Haupt, S., Montgomery, K. G., House, C. M., Azar, W. J., Pearson, H. B., Fisher, O. M., Read, M., Guerra, G. R., et al. (2017) · Nature Communications · doi:10.1038/ncomms14844 · Cited by 321
Cited by
Unsolved mysteries: How does lipid peroxidation cause ferroptosis?
Feng, H., & Stockwell, B. R. (2018) · PLOS Biology · doi:10.1371/journal.pbio.2006203 · Cited by 759
Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death
Battaglia, A. M., Chirillo, R., Aversa, I., Sacco, A., Costanzo, F., & Biamonte, F. (2020) · Cells · doi:10.3390/cells9061505 · Cited by 561
Mutant p53 in cancer: from molecular mechanism to therapeutic modulation
Chen, X., Zhang, T., Su, W., Dou, Z., Zhao, D., Jin, X., Lei, H., Wang, J., Xie, X., Cheng, B., et al. (2022) · Cell Death & Disease · doi:10.1038/s41419-022-05408-1 · Cited by 494
Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration
Masaldan, S., Bush, A. I., Devos, D., Rolland, A. S., & Moreau, C. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.033 · Cited by 481
The Role of Erastin in Ferroptosis and Its Prospects in Cancer Therapy
Zhao, Y., Li, Y., Zhang, R., Wang, F., Wang, T., & Jiao, Y. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s254995 · Cited by 458
Metadata
- Authors
- Gnanapradeepan, K., Basu, S., Barnoud, T., Budina-Kolomets, A., Kung, C.-P., & Murphy, M. E.
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2018-04-11
- Volume
- 9
- Pages
- 124-124
- ISSN
- 1664-2392 (ISSN-L)
- OpenAlex
- W2796592069
- Cited by
- 178
- References
- 9
- FWCI
- 13.19
- Type
- journal article
- Language
- en
- Open access
- gold
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