title: HSP40 interacts with pyruvate kinase M2 and regulates glycolysis and cell proliferation in tumor cells.
abstract: Pyruvate kinase M2 (PKM2) is predominantly expressed in cancers, which is considered as a key regulator of the Warburg effect. In this study, HSP40 was identified as a novel binding partner of PKM2. HSP40-PKM2 association destabilized PKM2 protein through HSC70. In the presence of HSP40, PKM2 protein level and PKM2-mediated PDK1 expression were down-regulated. Moreover, HSP40 was involved in regulating glucose metabolism on PKM2 dependent way and at the mean time had an effect on mitochondrial oxygen respiration. In line with inhibition effect of HSP40 on glycolysis, the growth of cancer cells was inhibited by HSP40.Our data provided a new regulation mechanism of PKM2, which suggested a new therapeutic target for cancer therapy.
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China; Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Liangqian
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China; Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D055550:Protein Stability; D011770:Pyruvate Kinase / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D050956:HSP40 Heat-Shock Proteins; D011770:Pyruvate Kinase; D005947:Glucose