title: Parkin Regulates the Activity of Pyruvate Kinase M2.
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.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center and Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center and Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China.
authors.forename: Fanzhou
authors.initials: F
authors.lastname: Li
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center and Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China.
authors.forename: Haichao
authors.initials: H
authors.lastname: Han
authors.affiliation: Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois 60637.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center and Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China.
authors.forename: Zebin
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Department of Genetics, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jianyuan
authors.initials: J
authors.lastname: Luo
authors.affiliation: Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois 60637.
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, and.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center and Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China, zhao6025729@bjmu.edu.cn.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhao
mesh_terms: D002460:Cell Line; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011770:Pyruvate Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D011770:Pyruvate Kinase; D005947:Glucose
keywords: Parkinson disease; glycolysis; parkin; pyruvate kinase; pyruvate kinase M2; ubiquitylation (ubiquitination)