Open AccessA cancer ubiquitome landscape identifies metabolic reprogramming as target of Parkin tumor suppression
Author(s) -
Ekta Agarwal,
Aaron R. Goldman,
HsinYao Tang,
Andrew V. Kossenkov,
Jagadish C. Ghosh,
Lucia R. Languino,
Valentina Vaira,
David W. Speicher,
Dario C. Altieri
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abg7287
Subject(s) - parkin , reprogramming , cancer , cancer research , biology , computational biology , bioinformatics , neuroscience , medicine , disease , genetics , gene , parkinson's disease
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.