Protein kinases regulate every aspect of cellular activity, whereas metabolic enzymes are responsible for energy production and catabolic and anabolic processes. Emerging evidence demonstrates that ...some metabolic enzymes, such as pyruvate kinase M2 (PKM2), phosphoglycerate kinase 1 (PGK1), ketohexokinase (KHK) isoform A (KHK-A), hexokinase (HK), and nucleoside diphosphate kinase 1 and 2 (NME1/2), that phosphorylate soluble metabolites can also function as protein kinases and phosphorylate a variety of protein substrates to regulate the Warburg effect, gene expression, cell cycle progression and proliferation, apoptosis, autophagy, exosome secretion, T cell activation, iron transport, ion channel opening, and many other fundamental cellular functions. The elevated protein kinase functions of these moonlighting metabolic enzymes in tumor development make them promising therapeutic targets for cancer.
In addition to their originally identified metabolic enzymatic activities, PKM2, PGK1, KHK-A, HK, and NDPK-A/B can act as protein kinases.
The protein kinase activity of metabolic enzymes phosphorylates a variety of protein substrates and regulates critical cellular activities.
Metabolic enzymes are often post-translationally modified, which changes their subcellular localization and allows them to phosphorylate protein substrates.
The protein kinase functions of metabolic enzymes make them promising therapeutic targets for cancer.
Pyruvate kinase M2 at a glance Yang, Weiwei; Lu, Zhimin
Journal of cell science,
05/2015, Letnik:
128, Številka:
9
Journal Article
Recenzirano
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Reprogrammed metabolism is a key feature of cancer cells. The pyruvate kinase M2 (PKM2) isoform, which is commonly upregulated in many human cancers, has been recently shown to play a crucial role in ...metabolism reprogramming, gene transcription and cell cycle progression. In this Cell Science at a glance article and accompanying poster, we provide a brief overview of recent advances in understanding the mechanisms underlying the regulation of PKM2 expression, enzymatic activity, metabolic functions and subcellular location. We highlight the instrumental role of the non-metabolic functions of PKM2 in tumorigenesis and evaluate the potential to target PKM2 for cancer treatment.
Lipid metabolism and cancer Bian, Xueli; Liu, Rui; Meng, Ying ...
The Journal of experimental medicine,
2021-Jan-04, Letnik:
218, Številka:
1
Journal Article
Recenzirano
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Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for biological membranes, and ...signaling molecules needed for proliferation, survival, invasion, metastasis, and response to the tumor microenvironment impact and cancer therapy. Here, we summarize and discuss current knowledge about the advances made in understanding the regulation of lipid metabolism in cancer cells and introduce different approaches that have been clinically used to disrupt lipid metabolism in cancer therapy.
Proline-directed phosphorylation is a posttranslational modification that is instrumental in regulating signaling from the plasma membrane to the nucleus, and its dysregulation contributes to cancer ...development. Protein interacting with never in mitosis A1 （Pinl）, which is overexpressed in many types of cancer, isomerizes specific phosphorylat- ed Ser/Thr-Pro bonds in many substrate proteins, including glycolytic enzyme, protein kinases, protein phosphatases, methyltransferase, lipid kinase, ubiquitin E3 ligase, DNA endonuclease, RNA polymerase, and transcription activa- tors and regulators. This Pinl-mediated isomerization alters the structures and activities of these proteins, thereby regulating cell metabolism, cell mobility, cell cycle progression, cell proliferation, cell survival, apoptosis and tumor development.
To accelerate our endeavors to overcome cancer,
Visualized Cancer Medicine
continues the previously launched program of publishing the 150 most important questions in cancer research and clinical ...oncology. In this article, three more questions are presented as follows: Question 102: Can non-glucose-based tumor imaging techniques facilitate tumor detection and metabolic classification? Question 103: how can we develop medicines to inhibit the cancer-specific metabolic functions of metabolic enzymes in tumors expressing wild-type IDH, without interfering with their canonical catalytic activities? Question 104: Can dietary-based cancer therapy be proven effective in treating cancer?
Highlights • PKM2 functions as a protein kinase to regulate gene expression. • PKM2 but not PKM1 translocates into the nucleus upon growth factor stimulation. • Nuclear PKM2 promotes growth ...factor-induced Warburg effect.
Metabolism and gene expression, which are two fundamental biological processes that are essential to all living organisms, reciprocally regulate each other to maintain homeostasis and regulate cell ...growth, survival and differentiation. Metabolism feeds into the regulation of gene expression via metabolic enzymes and metabolites, which can modulate chromatin directly or indirectly - through regulation of the activity of chromatin trans-acting proteins, including histone-modifying enzymes, chromatin-remodelling complexes and transcription regulators. Deregulation of these metabolic activities has been implicated in human diseases, prominently including cancer.
ERK1/2 is an important subfamily of mitogen‐activated protein kinases that control a broad range of cellular activities and physiological processes. ERK1/2 can be activated transiently or ...persistently by MEK1/2 and upstream MAP3Ks in conjunction with regulation and involvement of scaffolding proteins and phosphatases. Activation of ERK1/2 generally promotes cell survival; but under certain conditions, ERK1/2 can have pro‐apoptotic functions.
iubmb Life, 58: 621 ‐ 631, 2006
Pyruvate kinase M2 (PKM2) is upregulated in multiple cancer types and contributes to the Warburg effect by unclear mechanisms. Here we demonstrate that EGFR-activated ERK2 binds directly to PKM2 ...Ile 429/Leu 431 through the ERK2 docking groove and phosphorylates PKM2 at Ser 37, but does not phosphorylate PKM1. Phosphorylated PKM2 Ser 37 recruits PIN1 for cis-trans isomerization of PKM2, which promotes PKM2 binding to importin α5 and translocating to the nucleus. Nuclear PKM2 acts as a coactivator of β-catenin to induce c-Myc expression, resulting in the upregulation of GLUT1, LDHA and, in a positive feedback loop, PTB-dependent PKM2 expression. Replacement of wild-type PKM2 with a nuclear translocation-deficient mutant (S37A) blocks the EGFR-promoted Warburg effect and brain tumour development in mice. In addition, levels of PKM2 Ser 37 phosphorylation correlate with EGFR and ERK1/2 activity in human glioblastoma specimens. Our findings highlight the importance of nuclear functions of PKM2 in the Warburg effect and tumorigenesis.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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