Pyruvate kinase: Function, regulation and role in cancer.
Pyruvate kinase is an enzyme that catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP in glycolysis and plays a role in regulating cell metabolism. There are four mammalian pyruvate kinase isoforms with unique tissue expression patterns and regulatory properties. The M2 isoform of pyruvate kinase (PKM2) supports anabolic metabolism and is expressed both in cancer and normal tissue. The enzymatic activity of PKM2 is allosterically regulated by both intracellular signaling pathways and metabolites; PKM2 thus integrates signaling and metabolic inputs to modulate glucose metabolism according to the needs of the cell. Recent advances have increased our understanding of metabolic regulation by pyruvate kinase, raised new questions, and suggested the possibility of non-canonical PKM2 functions to regulate gene expression and cell cycle progression via protein-protein interactions and protein kinase activity. Here we review the structure, function, and regulation of pyruvate kinase and discuss how these properties enable regulation of PKM2 for cell proliferation and tumor growth.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: william.israelsen@utsouthwestern.edu.
William J
WJ
Israelsen
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: mvh@mit.edu.
Matthew G
MG
Vander Heiden
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology
D020033:Protein Isoforms; D011770:Pyruvate Kinase; D005947:Glucose
Cancer metabolism; PKM2; Pyruvate kinase