The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Mutant p53 protein localized in the cytoplasm inhibits autophagy
Open accessAbstract
The knockout, knockdown or chemical inhibition of p53 stimulates autophagy. Moreover, autophagy-inducing stimuli such as nutrient depletion, rapamycin or lithium cause the depletion of cytoplasmic p53, which in turn is required for the induction of autophagy. Here, we show that retransfection of p53(-/-) HCT 116 colon carcinoma cells with wild type p53 decreases autophagy down to baseline levels. Surprisingly, one third among a panel of 22 cancer-associated p53 single amino acid mutants also inhibited autophagy when transfected into p53(-/-) cells. Those variants of p53 that preferentially localize to the cytoplasm effectively repressed autophagy, whereas p53 mutants that display a prominently nuclear distribution failed to inhibit autophagy. The investigation of a series of deletion mutants revealed that removal of the DNA-binding domain from p53 fails to interfere with its role in the regulation of autophagy. Altogether, these results identify the cytoplasmic localization of p53 as the most important feature for p53-mediated autophagy inhibition. Moreover, the structural requirements for the two biological activities of extranuclear p53, namely induction of apoptosis and inhibition of autophagy, are manifestly different.
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“Many tumor-derived p53 mutants can also suppress autophagy, which might contribute to tumor progression by enhancing cell survival (Morselli et al., 2008; Tasdemir et al., 2008b).”
From p53 at a glance (2010) · cites this paper as Morselli et al., 2008
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LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Self-citationMathew, R., Karantza-Wadsworth, V., & White, E. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2254 · Cited by 1,798
Growth factor regulation of autophagy and cell survival in the absence of apoptosis
Lum, J. J., Bauer, D. E., Kong, M., Harris, M. H., Li, C., Lindsten, T., & Thompson, C. B. (2005) · Cell · doi:10.1016/j.cell.2004.11.046 · Cited by 1,487
DRAM, 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
Regulation of autophagy by cytoplasmic p53
Tasdemir, E., Maiuri, M. C., Galluzzi, L., Vitale, I., Djavaheri-Mergny, M., D'Amelio, M., Criollo, A., Morselli, E., Zhu, C., Harper, F., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1730 · Cited by 1,132
Self-citationDisruption of p53 in human cancer cells alters the responses to therapeutic agents.
Bunz, F., Hwang, P. M., Torrance, C., Waldman, T., Zhang, Y., Dillehay, L., Williams, J., Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6863 · Cited by 1,044
Acetylation of the p53 DNA-binding domain regulates apoptosis induction.
Sykes, S. M., Mellert, H. S., Holbert, M. A., Li, K., Marmorstein, R., Lane, W. S., & McMahon, S. B. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.11.026 · Cited by 752
Hot-spot mutants of p53 core domain evince characteristic local structural changes
Wong, K.-B., DeDecker, B. S., Freund, S. M. V., Proctor, M. R., Bycroft, M., & Fersht, A. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8438 · Cited by 221
Cited by
Blinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163
Mammalian autophagy: core molecular machinery and signaling regulation
Yang, Z., & Klionsky, D. J. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.11.014 · Cited by 1,956
Molecular Genetics of Colorectal Cancer
Fearon, E. R. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130235 · Cited by 1,805
Muller, P. A. J., & Vousden, K. H. (2013) · Nature Cell Biology · doi:10.1038/ncb2641 · Cited by 1,647
Mutant p53 in Cancer: New Functions and Therapeutic Opportunities
Muller, P. A. J., & Vousden, K. H. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.021 · Cited by 1,545
Metadata
- Authors
- Morselli, E., Tasdemir, E., Chiara Maiuri, M., Galluzzi, L., Kepp, O., Criollo, A., Vicencio, J. M., Soussi, T., & Kroemer, G.
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2008-10
- Volume
- 7
- Issue
- 19
- Pages
- 3056-3061
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2126993510
- Cited by
- 277
- References
- 9
- FWCI
- 12.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Morselli, E., Tasdemir, E., Chiara Maiuri, M., Galluzzi, L., Kepp, O., Criollo, A., Vicencio, J. M., Soussi, T., & Kroemer, G. (2008). Mutant p53 protein localized in the cytoplasm inhibits autophagy. Cell Cycle. https://doi.org/10.4161/cc.7.19.6751
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