Pyruvate Kinase M2: A Potential Target for Regulating inflammation

被引:148
作者
Alves-Filho, Jose C. [1 ]
Palsson-McDermott, Eva M. [2 ]
机构
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049 Ribeirao Preto, Brazil
[2] Trinity Coll Dublin, Sch Biochem & Immunol, Inst Biomed Sci, Dublin, Ireland
基金
巴西圣保罗研究基金会; 爱尔兰科学基金会;
关键词
PKM2; inflammation; HIF-1; alpha; glycolysis and oxidative phosphorylation; immunometabolism; cancer; HYPOXIA-INDUCIBLE FACTOR-1; PROTEIN-KINASE; CANCER-CELLS; NUCLEAR TRANSLOCATION; GENE-TRANSCRIPTION; GLUCOSE-METABOLISM; COLORECTAL-CANCER; CROHNS-DISEASE; PKM2; PROMOTES;
D O I
10.3389/fimmu.2016.00145
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Pyruvate kinase (PK) is the enzyme responsible for catalyzing the last step of glycolysis. Of the four PK isoforms expressed in mammalian cells, PKM2 has generated the most interest due to its impact on changes in cellular metabolism observed in cancer as well as in activated immune cells. As our understanding of dysregulated metabolism in cancer develops, and in light of the growing field of immunometabolism, intense efforts are in place to define the mechanism by which PKM2 regulates the metabolic profile of cancer as well as of immune cells. The enzymatic activity of PKM2 is heavily regulated by endogenous allosteric effectors as well as by intracellular signaling pathways, affecting both the enzymatic activity of PKM2 as a PK and the regulation of the recently described non-canonical nuclear functions of PKM2. We here review the current literature on PKM2 and its regulation, and discuss the potential for this protein as a therapeutic target in inflammatory disorders.
引用
收藏
页数:7
相关论文
共 69 条
[1]
Serine and glycine metabolism in cancer [J].
Amelio, Ivano ;
Cutruzzola, Francesca ;
Antonov, Alexey ;
Agostini, Massimiliano ;
Melino, Gerry .
TRENDS IN BIOCHEMICAL SCIENCES, 2014, 39 (04) :191-198
[2]
Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis [J].
Anastasiou, Dimitrios ;
Yu, Yimin ;
Israelsen, William J. ;
Jiang, Jian-Kang ;
Boxer, Matthew B. ;
Hong, Bum Soo ;
Tempel, Wolfram ;
Dimov, Svetoslav ;
Shen, Min ;
Jha, Abhishek ;
Yang, Hua ;
Mattaini, Katherine R. ;
Metallo, Christian M. ;
Fiske, Brian P. ;
Courtney, Kevin D. ;
Malstrom, Scott ;
Khan, Tahsin M. ;
Kung, Charles ;
Skoumbourdis, Amanda P. ;
Veith, Henrike ;
Southall, Noel ;
Walsh, Martin J. ;
Brimacombe, Kyle R. ;
Leister, William ;
Lunt, Sophia Y. ;
Johnson, Zachary R. ;
Yen, Katharine E. ;
Kunii, Kaiko ;
Davidson, Shawn M. ;
Christofk, Heather R. ;
Austin, Christopher P. ;
Inglese, James ;
Harris, Marian H. ;
Asara, John M. ;
Stephanopoulos, Gregory ;
Salituro, Francesco G. ;
Jin, Shengfang ;
Dang, Lenny ;
Auld, Douglas S. ;
Park, Hee-Won ;
Cantley, Lewis C. ;
Thomas, Craig J. ;
Heiden, Matthew G. Vander .
NATURE CHEMICAL BIOLOGY, 2012, 8 (10) :839-847
[3]
Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses [J].
Anastasiou, Dimitrios ;
Poulogiannis, George ;
Asara, John M. ;
Boxer, Matthew B. ;
Jiang, Jian-kang ;
Shen, Min ;
Bellinger, Gary ;
Sasaki, Atsuo T. ;
Locasale, Jason W. ;
Auld, Douglas S. ;
Thomas, Craig J. ;
Vander Heiden, Matthew G. ;
Cantley, Lewis C. .
SCIENCE, 2011, 334 (6060) :1278-1283
[4]
High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes [J].
Andersson, U ;
Wang, HC ;
Palmblad, K ;
Aveberger, AC ;
Bloom, O ;
Erlandsson-Harris, H ;
Janson, A ;
Kokkola, R ;
Zhang, MH ;
Yang, H ;
Tracey, KJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (04) :565-570
[5]
AN INVITRO NOVEL MECHANISM OF REGULATING THE ACTIVITY OF PYRUVATE KINASE-M2 BY THYROID-HORMONE AND FRUCTOSE-1,6-BISPHOSPHATE [J].
ASHIZAWA, K ;
MCPHIE, P ;
LIN, KH ;
CHENG, SY .
BIOCHEMISTRY, 1991, 30 (29) :7105-7111
[6]
Glutamine enema regulates colonic ubiquitinated proteins but not proteasome activities during TNBS-induced colitis leading to increased mitochondrial activity [J].
Bertrand, Julien ;
Marion-Letellier, Rachel ;
Azhar, Saida ;
Chan, Philippe ;
Legrand, Romain ;
Goichon, Alexis ;
Ghouzali, Ibtissem ;
Aziz, Moutaz ;
Vaudry, David ;
Savoye, Guillaume ;
Dechelotte, Pierre ;
Coeffier, Moise .
PROTEOMICS, 2015, 15 (13) :2198-2210
[7]
SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions [J].
Bhardwaj, Abhishek ;
Das, Sanjeev .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (05) :E538-E547
[8]
Bluemlein K, 2011, ONCOTARGET, V2, P393
[9]
Alteration of O-GlcNAcylation affects serine phosphorylation and regulates gene expression and activity of pyruvate kinase M2 in colorectal cancer cells [J].
Chaiyawat, Parunya ;
Chokchaichamnankit, Daranee ;
Lirdprapamongkol, Kriengsak ;
Srisomsap, Chantragan ;
Svasti, Jisnuson ;
Champattanachai, Voraratt .
ONCOLOGY REPORTS, 2015, 34 (04) :1933-1942
[10]
Serine is a natural ligand and allosteric activator of pyruvate kinase M2 [J].
Chaneton, Barbara ;
Hillmann, Petra ;
Zheng, Liang ;
Martin, Agnes C. L. ;
Maddocks, Oliver D. K. ;
Chokkathukalam, Achuthanunni ;
Coyle, Joseph E. ;
Jankevics, Andris ;
Holding, Finn P. ;
Vousden, Karen H. ;
Frezza, Christian ;
O'Reilly, Marc ;
Gottlieb, Eyal .
NATURE, 2012, 491 (7424) :458-+