Authors
Dimitrios Anastasiou, Yimin Yu, William J Israelsen, Jian-Kang Jiang, Matthew B Boxer, Bum Soo Hong, Wolfram Tempel, Svetoslav Dimov, Min Shen, Abhishek Jha, Hua Yang, Katherine R 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 R Johnson, Katharine E 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
Publication date
2012/10
Journal
Nature chemical biology
Volume
8
Issue
10
Pages
839-847
Publisher
Nature Publishing Group US
Description
Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active …
Total citations
Scholar articles
D Anastasiou, Y Yu, WJ Israelsen, JK Jiang, MB Boxer… - Nature chemical biology, 2012