Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis

Nature Chemical Biology - Tập 8 Số 10 - Trang 839-847 - 2012
Dimitrios Anastasiou1, Yimin Yu, William J. Israelsen, Joonsoo Kang, Matthew B. Boxer, Bum Soo Hong, W. Tempel, Svetoslav Dimov, Min Shen, Abhishek Jha, Hua Yang, Katherine Mattaini, Christian M. Metallo, Brian P. Fiske, Kevin D. Courtney, Scott Malstrom, Tahsin M. Khan, Charles Kung, Amanda P. Skoumbourdis, Henrike Veith, Noel Southall, Martin J. Walsh, Kyle R. Brimacombe, William Leister, Sophia Y. Lunt, Zachary Johnson, Katharine Yen, Kaiko Kunii, Shawn M. Davidson, Heather R. Christofk, Christopher P. Austin, James Inglese, Marian H. Harris, John M. Asara, Gregory Stephanopoulos, Francesco G. Salituro, Shengfang Jin, Lenny Dang, Douglas S. Auld, Hee‐Won Park, Lewis C. Cantley, Craig J. Thomas, Matthew G. Vander Heiden
1Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Tóm tắt

Từ khóa


Tài liệu tham khảo

Tennant, D.A., Duran, R.V. & Gottlieb, E. Targeting metabolic transformation for cancer therapy. Nat. Rev. Cancer 10, 267–277 (2010).

Vander Heiden, M.G. Targeting cancer metabolism: a therapeutic window opens. Nat. Rev. Drug Discov. 10, 671–684 (2011).

Vander Heiden, M.G., Cantley, L.C. & Thompson, C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033 (2009).

Cairns, R.A., Harris, I.S. & Mak, T.W. Regulation of cancer cell metabolism. Nat. Rev. Cancer 11, 85–95 (2011).

Levine, A.J. & Puzio-Kuter, A.M. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 330, 1340–1344 (2010).

Trachootham, D., Alexandre, J. & Huang, P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat. Rev. Drug Discov. 8, 579–591 (2009).

Weissleder, R. Molecular imaging in cancer. Science 312, 1168–1171 (2006).

Christofk, H.R. et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452, 230–233 (2008).

Mazurek, S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int. J. Biochem. Cell Biol. 43, 969–980 (2011).

Noguchi, T., Inoue, H. & Tanaka, T. The M1- and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing. J. Biol. Chem. 261, 13807–13812 (1986).

Clower, C.V. et al. The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc. Natl. Acad. Sci. USA 107, 1894–1899 (2010).

Yamada, K. & Noguchi, T. Regulation of pyruvate kinase M gene expression. Biochem. Biophys. Res. Commun. 256, 257–262 (1999).

Ikeda, Y., Tanaka, T. & Noguchi, T. Conversion of non-allosteric pyruvate kinase isozyme into an allosteric enzyme by a single amino acid substitution. J. Biol. Chem. 272, 20495–20501 (1997).

Ikeda, Y. & Noguchi, T. Allosteric regulation of pyruvate kinase M2 isozyme involves a cysteine residue in the intersubunit contact. J. Biol. Chem. 273, 12227–12233 (1998).

Ashizawa, K., Willingham, M.C., Liang, C.M. & Cheng, S.Y. 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, 16842–16846 (1991).

Ashizawa, K., McPhie, P., Lin, K.H. & Cheng, S.Y. An in vitro novel mechanism of regulating the activity of pyruvate kinase M2 by thyroid hormone and fructose 1, 6-bisphosphate. Biochemistry 30, 7105–7111 (1991).

Christofk, H.R., Vander Heiden, M.G., Wu, N., Asara, J.M. & Cantley, L.C. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452, 181–186 (2008).

Eigenbrodt, E., Reinacher, M., Scheefers-Borchel, U., Scheefers, H. & Friis, R. Double role for pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumor cells. Crit. Rev. Oncog. 3, 91–115 (1992).

Anastasiou, D. et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 334, 1278–1283 (2011).

Vander Heiden, M.G. et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329, 1492–1499 (2010).

Locasale, J.W., Vander Heiden, M.G. & Cantley, L.C. Rewiring of glycolysis in cancer cell metabolism. Cell Cycle 9, 4253 (2010).

Jiang, J.K. et al. 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, 3387–3393 (2010).

Boxer, M.B. et al. Evaluation of substituted N,N′-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. J. Med. Chem. 53, 1048–1055 (2010).

Ikeda, Y., Taniguchi, N. & Noguchi, T. Dominant negative role of the glutamic acid residue conserved in the pyruvate kinase M(1) isozyme in the heterotropic allosteric effect involving fructose-1,6-bisphosphate. J. Biol. Chem. 275, 9150–9156 (2000).

Kato, H., Fukuda, T., Parkison, C., McPhie, P. & Cheng, S.Y. Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase. Proc. Natl. Acad. Sci. USA 86, 7861–7865 (1989).

Hitosugi, T. et al. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci. Signal. 2, ra73 (2009).

Lv, L. et al. Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol. Cell 42, 719–730 (2011).

Luo, W. et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 145, 732–744 (2011).

Hoshino, A., Hirst, J.A. & Fujii, H. Regulation of cell proliferation by interleukin-3–induced nuclear translocation of pyruvate kinase. J. Biol. Chem. 282, 17706–17711 (2007).

Steták, A. et al. Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death. Cancer Res. 67, 1602–1608 (2007).

Hatzivassiliou, G. et al. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8, 311–321 (2005).

Vander Heiden, M.G. et al. Identification of small molecule inhibitors of pyruvate kinase M2. Biochem. Pharmacol. 79, 1118–1124 (2010).

Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. in Methods in Enzymology Vol. 276, 307–326 (Academic Press, 1997).

Minor, W., Cymborowski, M., Otwinowski, Z. & Chruszcz, M. HKL-3000: the integration of data reduction and structure solution—from diffraction images to an initial model in minutes. Acta Crystallogr. D Biol. Crystallogr. 62, 859–866 (2006).

Berman, H.M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235–242 (2000).

Schüttelkopf, A.W. & van Aalten, D.M. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr. D Biol. Crystallogr. 60, 1355–1363 (2004).

Emsley, P., Lohkamp, B., Scott, W.G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010).

Murshudov, G.N., Vagin, A.A. & Dodson, E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240–255 (1997).

Davis, I.W., Murray, L.W., Richardson, J.S. & Richardson, D.C. MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res. 32, W615–W619 (2004).

Schumacker, P.T., Chandel, N. & Agusti, A.G. Oxygen conformance of cellular respiration in hepatocytes. Am. J. Physiol. 265, L395–L402 (1993).

Metallo, C.M. et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 481, 380–384 (2011).

Yuan, M., Breitkopf, S.B., Yang, X. & Asara, J.M. A positive/negative ion-switching, targeted mass spectrometry-based metabolomics platform for bodily fluids, cells, and fresh and fixed tissue. Nat. Protoc. 7, 872–881 (2012).

Xia, J., Mandal, R., Sinelnikov, I.V., Broadhurst, D. & Wishart, D.S. MetaboAnalyst 2.0–a comprehensive server for metabolomic data analysis. Nucleic Acids Res. W127–W133 (2012).