Abstract
Cancer cells are characterized by reprogramming of energy metabolism. Over the last decade, understanding of the metabolic changes that occur in cancer has increased dramatically, with great interest in targeting metabolism for cancer therapy. Pyruvate kinase isoenzyme type M2 (abbreviations: PKM2, M2-PK) plays a key role in modulating glucose metabolism to support cell proliferation. PKM2, like other PK isoforms, catalyzes the last energy-generating step in glycolysis, but is unique in its capacity to be regulated. PKM2 is regulated at several cellular levels, including gene expression, alternative splicing and post-translational modification. In addition, PKM2 is regulated by key metabolic intermediates and interacts with more than twenty different proteins. Hence, this isoenzyme is an important regulator of glycolysis, and additionally functions in other novel roles that have recently emerged. Recent evidence indicates that intervening with the complex regulatory network of PKM2 has severe consequences on tumor cell proliferation, indicating the potential of this enzyme as a target for tumor therapy.
Keywords: Pyruvate Kinase M2 (PKM2), Cancer therapeutics, Cancer Metabolism, PKM2 regulation, alternative splicing, post-translational modification, glycolysis, network.
Current Pharmaceutical Design
Title:Pyruvate Kinase M2: Regulatory Circuits and Potential for Therapeutic Intervention
Volume: 20 Issue: 15
Author(s): Vibhor Gupta, Kathryn E. Wellen, Sybille Mazurek and Rameshwar N. K. Bamezai
Affiliation:
Keywords: Pyruvate Kinase M2 (PKM2), Cancer therapeutics, Cancer Metabolism, PKM2 regulation, alternative splicing, post-translational modification, glycolysis, network.
Abstract: Cancer cells are characterized by reprogramming of energy metabolism. Over the last decade, understanding of the metabolic changes that occur in cancer has increased dramatically, with great interest in targeting metabolism for cancer therapy. Pyruvate kinase isoenzyme type M2 (abbreviations: PKM2, M2-PK) plays a key role in modulating glucose metabolism to support cell proliferation. PKM2, like other PK isoforms, catalyzes the last energy-generating step in glycolysis, but is unique in its capacity to be regulated. PKM2 is regulated at several cellular levels, including gene expression, alternative splicing and post-translational modification. In addition, PKM2 is regulated by key metabolic intermediates and interacts with more than twenty different proteins. Hence, this isoenzyme is an important regulator of glycolysis, and additionally functions in other novel roles that have recently emerged. Recent evidence indicates that intervening with the complex regulatory network of PKM2 has severe consequences on tumor cell proliferation, indicating the potential of this enzyme as a target for tumor therapy.
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Gupta Vibhor, Wellen E. Kathryn, Mazurek Sybille and Bamezai K. Rameshwar N., Pyruvate Kinase M2: Regulatory Circuits and Potential for Therapeutic Intervention, Current Pharmaceutical Design 2014; 20 (15) . https://dx.doi.org/10.2174/13816128113199990484
DOI https://dx.doi.org/10.2174/13816128113199990484 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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