Beclin1 Controls the Levels of p53 by Regulating the Deubiquitination Activity of USP10 and USP13

By Junli Liu, Hongguang Xia, Minsu Kim, Li-hua Xu, Y. Li, Lihong Zhang, Yu Cai, H. Norberg, Tao Zhang, T. Furuya and 10 more. Cell, 2011

796 citations recorded by the source corpus.

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.

Subfields: Cell Biology, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1db839c581d42886db256d1e6c065b9733e0603b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. Alec C. Kimmelman
2. Sang Hun Lee
3. C. Yun
4. E. White

In Epidemiology

1. Alec C. Kimmelman
2. R. Amaravadi
3. E. White
4. Sang Hun Lee
5. C. Yun
6. Guido Kroemer
7. Beth Levine
8. Chang S. Chan

In Molecular Biology

1. Alec C. Kimmelman
2. R. Amaravadi
3. Sang Hun Lee
4. C. Yun
5. E. White
6. Guido Kroemer
7. Y. Fouad
8. C. Aanei

Citations in the corpus

• The Roles of Autophagy in Cancer (2018, background): “Spautin-1 inhibits autophagy and leads to the induction of proteasomal removal of class III PI3K kinase complexes [177].”
• Recent insights into the function of autophagy in cancer (2016, background): “A fluorescent LC3 high-content, image-based screen identified Spautin-1 as an autophagy inhibitor (Liu et al. 2011).”