Document Type
Article
Publication Date
8-25-2021
Abstract
Changes in metabolism that affect mitochondrial and glycolytic networks are hallmarks of cancer, but their impact in disease is still elusive. Using global proteomics and ubiquitome screens, we now show that Parkin, an E3 ubiquitin ligase and key effector of mitophagy altered in Parkinson's disease, shuts off mitochondrial dynamics and inhibits the non-oxidative phase of the pentose phosphate pathway. This blocks tumor cell movements, creates metabolic and oxidative stress, and inhibits primary and metastatic tumor growth. Uniformly down-regulated in cancer patients, Parkin tumor suppression requires its E3 ligase function, is reversed by antioxidants, and is independent of mitophagy. These data demonstrate that cancer metabolic networks are potent oncogenes directly targeted by endogenous tumor suppression.
Recommended Citation
Agarwal, Ekta; Goldman, Aaron R; Tang, Hsin-Yao; Kossenkov, Andrew V; Ghosh, Jagadish C; Languino, Lucia; Vaira, Valentina; Speicher, David W; and Altieri, Dario C, "A cancer ubiquitome landscape identifies metabolic reprogramming as target of Parkin tumor suppression" (2021). Department of Cancer Biology Faculty Papers. Paper 183.
https://jdc.jefferson.edu/cbfp/183
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
PubMed ID
34433563
Language
English
Comments
This article is the author’s final published version in Science Advances, Volume 7, Issue 35, August 2021, Article number eabg7287.
The published version is available at https://doi.org/10.1126/sciadv.abg7287. Copyright © Agarwal et al.