HSP40 interacts with pyruvate kinase M2 and regulates glycolysis and cell proliferation in tumor cells

Liangqian Huang; Zhenhai Yu; Teng Zhang; Xiaoping Zhao; Gang Huang

doi:10.1371/journal.pone.0092949

HSP40 interacts with pyruvate kinase M2 and regulates glycolysis and cell proliferation in tumor cells

PLoS One. 2014 Mar 21;9(3):e92949. doi: 10.1371/journal.pone.0092949. eCollection 2014.

Authors

Liangqian Huang¹, Zhenhai Yu², Teng Zhang³, Xiaoping Zhao³, Gang Huang⁴

Affiliations

¹ 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.
² School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carrier Proteins / metabolism
Cell Line
Cell Line, Tumor
Cell Proliferation
Glucose / metabolism
Glycolysis
HSP40 Heat-Shock Proteins / metabolism*
Humans
Neoplasms / metabolism*
Protein Binding
Protein Interaction Mapping
Protein Stability
Pyruvate Kinase / metabolism*

Substances

Carrier Proteins
HSP40 Heat-Shock Proteins
Pyruvate Kinase
Glucose

Grants and funding

The study was supported by research grants from “973” Project (No. 2012CB932604), New Drug Discovery Project (No. 2012ZX09506-001-005), Shanghai Leading Academic Discipline Project (No. S30203), National Natural Science Foundation of China (No. 81071180,81001008 & 81372195), Shanghai Pujiang Program (No. 13PJ1406000) and Science and Technology Commission of Shanghai Municipality (No. 134119a5600). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.