M2 pyruvate kinase provides a mechanism for nutrient sensing and regulation of cell proliferation

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 15, 2013, Pages 5881-5886

  Morgan, Hugh P ^a   O'Reilly, Francis J ^a   Wear, Martin A ^a   Robert O'Neill, J ^a   Fothergill Gilmore, Linda A ^a   Hupp, Ted ^a   Walkinshaw, Malcolm D ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Allosteric regulation; Nutrient sensor; Thyroid hormone T3; Warburg effect

Indexed keywords

AMINO ACID; FRUCTOSE 1,6 BISPHOSPHATE; GLUCOSE; LIOTHYRONINE; LYSINE; MONOMER; PHENYLALANINE; PYRUVATE KINASE; PYRUVATE KINASE ISOENZYME M 2; TETRAMER; THYROID HORMONE; UNCLASSIFIED DRUG;

ALLOSTERISM; ARTICLE; CELL PROLIFERATION; CELL STRAIN HCT116; MOLECULAR MECHANICS; NUTRIENT; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN INTERACTION; PROTEIN STRUCTURE; REGULATORY MECHANISM; SIGNAL TRANSDUCTION;

ALLOSTERIC SITE; AMINO ACID SEQUENCE; CATALYTIC DOMAIN; CELL LINE, TUMOR; CELL PROLIFERATION; CRYSTALLOGRAPHY, X-RAY; DIMERIZATION; HUMANS; INHIBITORY CONCENTRATION 50; MOLECULAR SEQUENCE DATA; PHENYLALANINE; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; PYRUVATE KINASE; TRIIODOTHYRONINE;

EID: 84876058530     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1217157110     Document Type: Article

References (41)

1. Yamada K, Noguchi T (1999) Nutrient and hormonal regulation of pyruvate kinase gene expression. Biochem J 337(Pt 1):1-11.
2. Dombrauckas JD, Santarsiero BD, Mesecar AD (2005) Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis. Biochemistry 44(27):9417-9429.
3. Christofk HR, et al. (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452(7184):230-233.
4. Bluemlein K, et al. (2011) No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis. Oncotarget 2(5):393-400.
5. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 324(5930):1029-1033.
6. Mazurek S (2011) Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol 43(7):969-980.
7. Locasale JW, Cantley LC (2011) Metabolic flux and the regulation of mammalian cell growth. Cell Metab 14(4):443-451.
8. Lv L, et al. (2011) Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell 42(6):719-730.
9. Hitosugi T, et al. (2009) Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal 2(97):ra73.
10. Anastasiou D, et al. (2011) Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 334(6060):1278-1283.
11. Luo W, et al. (2011) Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxiainducible factor 1. Cell 145(5):732-744.
12. Mazurek S, Zwerschke W, Jansen-Dürr P, Eigenbrodt E (2001) Effects of the human papilloma virus HPV-16 E7 oncoprotein on glycolysis and glutaminolysis: Role of pyruvate kinase type M2 and the glycolytic-enzyme complex. Biochem J 356(Pt 1):247-256.
13. Zwerschke W, et al. (1999) Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc Natl Acad Sci USA 96(4):1291-1296.
14. Steták A, et al. (2007) Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death. Cancer Res 67(4):1602-1608.
15. Boxer MB, et al. (2010) Evaluation of substituted N, N'- diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. J Med Chem 53(3):1048-1055.
16. Jiang JK, et al. (2010) Evaluation of thieno[3, 2-b]pyrrole[3, 2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase. Bioorg Med Chem Lett 20(11):3387-3393.
17. Vander Heiden MG, et al. (2010) Identification of small molecule inhibitors of pyruvate kinase M2. Biochem Pharmacol 79(8):1118-1124.
18. Flory W, Peczon BD, Koeppe RE, Spivey HO (1974) Kinetic properties of rat liver pyruvate kinase at cellular concentrations of enzyme, substrates and modifiers. Biochem J 141(1):127-131.
19. Burton RL, Chen S, Xu XL, Grant GA (2009) Transient kinetic analysis of the interaction of L-serine with Escherichia coli D-3-phosphoglycerate dehydrogenase reveals the mechanism of V-type regulation and the order of effector binding. Biochemistry 48(51):12242-12251.
20. Kato H, Fukuda T, Parkison C, McPhie P, Cheng SY (1989) Cytosolic thyroid hormonebinding protein is a monomer of pyruvate kinase. Proc Natl Acad Sci USA 86(20):7861-7865.
21. Ashizawa K, Willingham MC, Liang CM, Cheng SY (1991) In vivo regulation of monomer-tetramer conversion of pyruvate kinase subtype M2 by glucose is mediated via fructose 1, 6-bisphosphate. J Biol Chem 266(25):16842-16846.
22. Ashizawa K, McPhie P, Lin KH, Cheng SY (1991) An in vitro novel mechanism of regulating the activity of pyruvate kinase M2 by thyroid hormone and fructose 1, 6-bisphosphate. Biochemistry 30(29):7105-7111.
23. Larsen TM, Benning MM, Rayment I, Reed GH (1998) Structure of the bis (Mg2+)-ATP-oxalate complex of the rabbit muscle pyruvate kinase at 2.1 A resolution: ATP binding over a barrel. Biochemistry 37(18):6247-6255.
24. Morgan HP, et al. (2010) Allosteric mechanism of pyruvate kinase from Leishmania mexicana uses a rock and lock model. J Biol Chem 285(17):12892-12898.
25. Consler TG, Woodard SH, Lee JC (1989) Effects of primary sequence differences on the global structure and function of an enzyme: A study of pyruvate kinase isozymes. Biochemistry 28(22):8756-8764.
26. Williams R, Holyoak T, McDonald G, Gui C, Fenton AW (2006) Differentiating a ligand's chemical requirements for allosteric interactions from those for protein binding. Phenylalanine inhibition of pyruvate kinase. Biochemistry 45(17):5421-5429.
27. Kumar Y, et al. (2010) In vivo factors influencing tumour M2-pyruvate kinase level in human pancreatic cancer cell lines. Tumour Biol 31(2):69-77.
28. Mazurek S, Eigenbrodt E (2003) The tumor metabolome. Anticancer Res 23(2 A):1149-1154.
29. Eigenbrodt E, Reinacher M, Scheefers-Borchel U, Scheefers H, Friis R (1992) Double role for pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumor cells. Crit Rev Oncog 3(1-2):91-115.
30. Zhou CF, et al. (2012) Pyruvate kinase type M2 is upregulated in colorectal cancer and promotes proliferation and migration of colon cancer cells. IUBMB Life 64(9):775-782.
31. Hardin CD, Roberts TM (1994) Metabolism of exogenously applied fructose 1, 6-bisphosphate in hypoxic vascular smooth muscle. Am J Physiol 267(6 Pt 2):H2325-H2332.
32. Chaneton B, et al. (2012) Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 491(7424):458-462.
33. Walsh MJ, et al. (2011) 2-Oxo-N-aryl-1, 2, 3, 4-tetrahydroquinoline-6- sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. Bioorg Med Chem Lett 21(21):6322-6327.
34. Anastasiou D, et al. (2012) Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol 8(10):839-847.
35. Cheng SY, Leonard JL, Davis PJ (2010) Molecular aspects of thyroid hormone actions. Endocr Rev 31(2):139-170.
36. Suhane S, Ramanujan VK (2011) Thyroid hormone differentially modulates Warburg phenotype in breast cancer cells. Biochem Biophys Res Commun 414(1):73-78.
37. Lopes RP, et al. (2006) The effects of fructose-1, 6-bisphosphate and dexamethasone on acute inflammation and T-cell proliferation. Inflamm Res 55(8):354-358.
38. Christofk HR, Van der Heiden MG, Wu N, Asara JM, Cantley LC (2008) Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452(7184):181-186.
39. Demopoulos HB (1966) Effects of low phenylalanine-tyrosine diets on S91 mouse melanomas. J Natl Cancer Inst 37(2):185-190.
40. Mitamura A, Yuen T, Duke PS, Demopoulos HB (1966) Ultrastructure of S-91 mouse melanomas subjected to phenylalanine and tyrosine restriction in vivo. Am J Pathol 49(2):309-324.
41. Lechner JF (1984) Interdependent regulation of epithelial cell replication by nutrients, hormones, growth factors, and cell density. Fed Proc 43(1):116-120.