A cancer ubiquitome landscape identifies metabolic reprogramming as target of Parkin tumor suppression

Ekta Agarwal, Aaron R. Goldman, Hsin Yao Tang, Andrew V. Kossenkov, Jagadish C. Ghosh, Lucia R. Languino, Valentina Vaira, David W. Speicher, Dario C. Altieri

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbereabg7287
JournalScience advances
Volume7
Issue number35
DOIs
Publication statusPublished - Aug 2021

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'A cancer ubiquitome landscape identifies metabolic reprogramming as target of Parkin tumor suppression'. Together they form a unique fingerprint.

Cite this