Parkin regulates the activity of pyruvate kinase M2

Kun Liu, Fanzhou Li, Haichao Han, Yue Chen, Zebin Mao, Jianyuan Luo, Yingming Zhao, Bin Zheng, Wei Gu, Wenhui Zhao

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Parkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification. We found that parkin interacts with PKM2 both in vitro and in vivo, and this interaction dramatically increases during glucose starvation. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. Parkin regulates the glycolysis pathway and affects the cell metabolism. Our studies revealed the novel important roles of parkin in tumor cell metabolism and provided new insight for therapy of Parkinson disease.

Original languageEnglish (US)
Pages (from-to)10307-10317
Number of pages11
JournalJournal of Biological Chemistry
Volume291
Issue number19
DOIs
StatePublished - May 6 2016

Bibliographical note

Funding Information:
Supported by Peking University Health Science Center Initial Aid Grant BMU20140379.

Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.

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