The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Beclin1 Controls the Levels of p53 by Regulating the Deubiquitination Activity of USP10 and USP13
Open accessAbstract
SUMMARY Autophagy is an important intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles. We report a potent small molecule inhibitor of autophagy named “spautin-1” for specific and potent autophagy inhibitor-1. Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Beclin1 is a tumor suppressor and frequently monoallelically lost in human cancers. Interestingly, Beclin1 also controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities. Since USP10 mediates the deubiquitination of p53, regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. Our study provides a molecular mechanism involving protein deubiquitination that connects two important tumor suppressors, p53 and Beclin1, and a potent small molecule inhibitor of autophagy as a possible lead compound for developing anticancer drugs.
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Cites
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Induction of autophagy and inhibition of tumorigenesis by beclin 1
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Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
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Self-citationYue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116
Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes
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Autophagy-deficient mice develop multiple liver tumors
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USP10 Regulates p53 Localization and Stability by Deubiquitinating p53
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“Regulation of p53 via Vps34 Complexes and Deubiquitination Since USP10 is known as a deubiquitinating protease of p53 (Yuan et al., 2010), inhibition of USP10 by spautin-1 may promote the degradation of p53.”
MethodInfluentialSelf-citation
Cited by
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
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Self-citationCellular quality control by the ubiquitin–proteasome system and autophagy
Pohl, C., & Dikic, I. (2019) · Science · doi:10.1126/science.aax3769 · Cited by 1,212
The Roles of Autophagy in Cancer
Yun, C. W., & Lee, S. H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113466 · Cited by 965
Deubiquitylating enzymes and drug discovery: emerging opportunities
Harrigan, J. A., Jacq, X., Martin, N. M., & Jackson, S. P. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.152 · Cited by 940
Metadata
- Authors
- Liu, J., Xia, H., Kim, M., Xu, L., Li, Y., Zhang, L., Cai, Y., Norberg, H. V., Zhang, T., Furuya, T., Jin, M., Zhu, Z., Wang, H., Yu, J., Li, Y., Hao, Y., Choi, A., Ke, H., Ma, D., & Yuan, J.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 147
- Issue
- 1
- Pages
- 223-234
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2098264151
- Cited by
- 820
- References
- 11
- FWCI
- 15.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Liu, J., Xia, H., Kim, M., Xu, L., Li, Y., Zhang, L., Cai, Y., Norberg, H. V., Zhang, T., Furuya, T., Jin, M., Zhu, Z., Wang, H., Yu, J., Li, Y., Hao, Y., Choi, A., Ke, H., Ma, D., & Yuan, J. (2011). Beclin1 Controls the Levels of p53 by Regulating the Deubiquitination Activity of USP10 and USP13. Cell. https://doi.org/10.1016/j.cell.2011.08.037
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