The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
p53-dependent regulation of autophagy protein LC3 supports cancer cell survival under prolonged starvation
Open accessAbstract
The p53 tumor suppressor is mutated in a high percentage of human tumors. However, many other tumors retain wild-type (wt) p53 expression, raising the intriguing possibility that they actually benefit from it. Recent studies imply a role for p53 in regulation of autophagy, a catabolic pathway by which eukaryotic cells degrade and recycle macromolecules and organelles, particularly under conditions of nutrient deprivation. Here, we show that, in many cell types, p53 confers increased survival in the face of chronic starvation. We implicate regulation of autophagy in this effect. In HCT116 human colorectal cancer cells exposed to prolonged nutrient deprivation, the endogenous wt p53 posttranscriptionally down-regulates LC3, a pivotal component of the autophagic machinery. This enables reduced, yet sustainable autophagic flux. Loss of p53 impairs autophagic flux and causes excessive LC3 accumulation upon starvation, culminating in apoptosis. Thus, p53 increases cell fitness by maintaining better autophagic homeostasis, adjusting the rate of autophagy to changing circumstances. We propose that some cancer cells retain wt p53 to benefit from the resultant increased fitness under limited nutrient supply.
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“One study showed that p53 regulates autophagy through LC3.119”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [119]
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LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
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Self-citationReactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
Scherz‐Shouval, R., Shvets, E., Fass, E., Shorer, H., Gil, L., & Elazar, Z. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601623 · Cited by 2,101 · cited 1×
“2A, levels of mRNA encoding LC3B, one of the three human LC3 isoforms, did not change on very short starvation, as reported earlier (25).”
BackgroundSelf-citationThe first 30 years of p53: growing ever more complex.
Levine, A. J., & Oren, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2723 · Cited by 1,967
Self-citationDRAM, a p53-Induced Modulator of Autophagy, Is Critical for Apoptosis
Crighton, D., Wilkinson, S., O'Prey, J., Syed, N., Smith, P., Harrison, P. R., Gasco, M., Garrone, O., Crook, T., & Ryan, K. M. (2006) · Cell · doi:10.1016/j.cell.2006.05.034 · Cited by 1,380
p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling
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Cited by
Kenzelmann Broz, D., Spano Mello, S., Bieging, K. T., Jiang, D., Dusek, R. L., Brady, C. A., Sidow, A., & Attardi, L. D. (2013) · Genes & Development · doi:10.1101/gad.212282.112 · Cited by 443
Foxk proteins repress the initiation of starvation-induced atrophy and autophagy programs
Bowman, C. J., Ayer, D. E., & Dynlacht, B. D. (2014) · Nature Cell Biology · doi:10.1038/ncb3062 · Cited by 153
Autophagic activity dictates the cellular response to oncogenic RAS
Wang, Y., Wang, X. D., Lapi, E., Sullivan, A., Jia, W., He, Y.-W., Ratnayaka, I., Zhong, S., Goldin, R. D., Goemans, C. G., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120193109 · Cited by 117
Wang, S.-J., Yu, G., Jiang, L., Li, T., Lin, Q., Tang, Y., & Gu, W. (2013) · Cell Cycle · doi:10.4161/cc.23597 · Cited by 54
p53: from understanding its structure to advances in therapeutic targeting
Wang, W., Liu, X., Liu, H., Abolhassani, H., Yan, H., Zhang, H., & Wang, X. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02549-5 · Cited by 30
Metadata
- Authors
- Scherz-Shouval, R., Weidberg, H., Gonen, C., Wilder, S., Elazar, Z., & Oren, M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-10-11
- Volume
- 107
- Issue
- 43
- Pages
- 18511-18516
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1998192361
- Cited by
- 235
- References
- 11
- FWCI
- 11.32
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Scherz-Shouval, R., Weidberg, H., Gonen, C., Wilder, S., Elazar, Z., & Oren, M. (2010). p53-dependent regulation of autophagy protein LC3 supports cancer cell survival under prolonged starvation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1006124107
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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
