Pyruvate kinase M2: A simple molecule with complex functions

被引：126

作者：

Alquraishi, Mohammed ^{[1
]}

Puckett, Dexter L. ^{[1
]}

Alani, Dina S. ^{[1
]}

Humidat, Amal S. ^{[1
]}

Frankel, Victoria D. ^{[1
]}

Donohoe, Dallas R. ^{[1
]}

Whelan, Jay ^{[1
]}

Bettaieb, Ahmed ^{[1
,2
,3
]}

机构：

[1] Univ Tennessee, Dept Nutr, Knoxville, TN 37996 USA

[2] Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA

[3] Univ Tennessee, Grad Sch Genome Sci & Technol, Knoxville, TN 37996 USA

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2019年 / 143卷

关键词：

Pyruvate kinase M2; Glycolysis; Warburg effect; Cancer; Redox homeostasis; Oxidants; Inflammation; Metabolic diseases; ACTIVATED PROTEIN-KINASE; NUCLEAR TRANSLOCATION; INSULIN-RESISTANCE; AEROBIC GLYCOLYSIS; ENERGY-METABOLISM; NITRIC-OXIDE; PROMOTES PROLIFERATION; GLUCOSE-METABOLISM; GENE-TRANSCRIPTION; CANCER METABOLISM;

D O I：

10.1016/j.freeradbiomed.2019.08.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pyruvate kinase M2 is a critical enzyme that regulates cell metabolism and growth under different physiological conditions. In its metabolic role, pyruvate kinase M2 catalyzes the last glycolytic step which converts phosphoenolpyruvate to pyruvate with the generation of ATP. Beyond this metabolic role in glycolysis, PKM2 regulates gene expression in the nucleus, phosphorylates several essential proteins that regulate major cell signaling pathways, and contribute to the redox homeostasis of cancer cells. The expression of PKM2 has been demonstrated to be significantly elevated in several types of cancer, and the overall inflammatory response. The unusual pattern of PKM2 expression inspired scientists to investigate the unrevealed functions of PKM2 and the therapeutic potential of targeting PKM2 in cancer and other disorders. Therefore, the purpose of this review is to discuss the mechanistic and therapeutic potential of targeting PKM2 with the focus on cancer metabolism, redox homeostasis, inflammation, and metabolic disorders. This review highlights and provides insight into the metabolic and non-metabolic functions of PKM2 and its relevant association with health and disease.

引用

页码：176 / 192

页数：17

共 209 条

[1] CARM1 suppresses de novo serine synthesis by promoting PKM2 activity [J].

Abeywardana, Tharindumala ;

Oh, Myungeun ;

Jiang, Lei ;

Yang, Ying ;

Kong, Mei ;

Song, Jikui ;

Yang, Yanzhong .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2018, 293 (39) :15290-15303

[2] NALP3 forms an IL-lβ-Processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder [J].

Agostini, L ;

Martinon, F ;

Burns, K ;

McDermott, MF ;

Hawkins, PN ;

Tschopp, J .

IMMUNITY, 2004, 20 (03) :319-325

[3] Elevation of serum pyruvate kinase M2 (PKM2) in IBD and its relationship to IBD indices [J].

Almousa, Ahmed A. ;

Morris, Marc ;

Fowler, Sharyle ;

Jones, Jennifer ;

Alcorn, Jane .

CLINICAL BIOCHEMISTRY, 2018, 53 :19-24

[4] Pyruvate Kinase M2: A Potential Target for Regulating inflammation [J].

Alves-Filho, Jose C. ;

Palsson-McDermott, Eva M. .

FRONTIERS IN IMMUNOLOGY, 2016, 7

[5] Small ubiquitin-like modifier 1 modification of pyruvate kinase M2 promotes aerobic glycolysis and cell proliferation in A549 human lung cancer cells [J].

An, Shuxian ;

Huang, Liangqin ;

Miao, Ping ;

Shi, Liang ;

Shen, Mengqin ;

Zhao, Xiaoping ;

Liu, Jianjun ;

Huang, Gang .

ONCOTARGETS AND THERAPY, 2018, 11 :2097-2109

[6] 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

[7] 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

[8] Effects of PKM2 Gene Silencing on the Proliferation and Apoptosis of Colorectal Cancer LS-147T and SW620 Cells (Publication with Expression of Concern. See vol. 55, pg. 677, 2021) [J].

Ao, Ran ;

Guan, Lin ;

Wang, Ying ;

Wang, Jia-Ni .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2017, 42 (05) :1769-1778

[9] MDM2 controls gene expression independently of p53 in both normal and cancer cells [J].

Arena, Giuseppe ;

Riscal, Romain ;

Linares, Laetitia K. ;

Le Cam, Laurent .

CELL DEATH AND DIFFERENTIATION, 2018, 25 (09) :1533-1535

[10] Oxidative Phosphorylation as an Emerging Target in Cancer Therapy [J].

Ashton, Thomas M. ;

McKenna, W. Gillies ;

Kunz-Schughart, Leoni A. ;

Higgins, Geoff S. .

CLINICAL CANCER RESEARCH, 2018, 24 (11) :2482-2490

← 1 2 3 4 5 6 7 8 9 10 →