AMPK and cell proliferation – AMPK as a therapeutic target for atherosclerosis and cancer
TLDR
Observations suggest that AMPK activation is a logical therapeutic target for diseases rooted in cellular proliferation, including atherosclerosis and cancer.Abstract:
AMPK is a serine/threonine protein kinase, which serves as an energy sensor in all eukaryotic cell types. Published studies indicate that AMPK activation strongly suppresses cell proliferation in non-malignant cells as well as in tumour cells. These actions of AMPK appear to be mediated through multiple mechanisms including regulation of the cell cycle and inhibition of protein synthesis, de novo fatty acid synthesis, specifically the generation of mevalonate as well as other products downstream of mevalonate in the cholesterol synthesis pathway. Cell cycle regulation by AMPK is mediated by up-regulation of the p53–p21 axis as well as regulation of TSC2–mTOR (mammalian target of rapamycin) pathway. The AMPK signalling network contains a number of tumour suppressor genes including LKB1, p53, TSC1 and TSC2, and overcomes growth factor signalling from a variety of stimuli (via growth factors and by abnormal regulation of cellular proto-oncogenes including PI3K, Akt and ERK). These observations suggest that AMPK activation is a logical therapeutic target for diseases rooted in cellular proliferation, including atherosclerosis and cancer. In this review, we discuss about exciting recent advances indicating that AMPK functions as a suppressor of cell proliferation by controlling a variety of cellular events in normal cells as well as in tumour cells.read more
Citations
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p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling
Andrei V. Budanov,Michael Karin +1 more
TL;DR: Sestrin1 and Sestrin2 provide an important link between genotoxic stress, p53 and the mTOR signaling pathway and are demonstrated to activate the AMP-responsive protein kinase (AMPK) and target it to phosphorylate TSC2 and stimulate its GAP activity, thereby inhibiting mTOR.
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Resveratrol stimulates AMP kinase activity in neurons.
TL;DR: It is shown that resveratrol activated AMPK in Neuro2a cells and primary neurons in vitro as well as in the brain, suggesting that neuronal activation of AMPK by resver atrol could affect neuronal energy homeostasis and contribute to the neuroprotective effects of resverAtrol.
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Regulation of Immune Responses by mTOR
TL;DR: The ability of m TOR to direct the adaptive immune response is discussed and the role of mTOR in promoting differentiation, activation, and function in T cells, B cells, and antigen-presenting cells is examined.
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Adenosine 5′-Monophosphate-Activated Protein Kinase Promotes Macrophage Polarization to an Anti-Inflammatory Functional Phenotype
TL;DR: A role of AMP-activated protein kinase (AMPK) as a potent counterregulator of inflammatory signaling pathways in macrophages is demonstrated and it is found that AMPK negatively regulated LPS-induced IκB-α degradation and positively regulated Akt activation, accompanied by inhibition of glycogen synthase kinase β and activation of CREB.
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Glucose metabolism and cancer.
TL;DR: This work has shown that activation of the hypoxia-inducible factor (HIF) is a common consequence of a wide variety of mutations underlying human cancer, and proposed therapeutic strategies based on modulation of AMPK, HIF and other metabolic targets have been proposed to exploit the addiction of tumor cells to increased glucose uptake and glycolysis.
References
More filters
Journal ArticleDOI
Cancer Cell Cycles
TL;DR: Genetic alterations affecting p16INK4a and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development.
Journal ArticleDOI
The phosphoinositide 3-kinase pathway.
TL;DR: The PI3K pathway is implicated in human diseases including diabetes and cancer, and understanding the intricacies of this pathway may provide new avenues for therapuetic intervention.
Journal ArticleDOI
Role of AMP-activated protein kinase in mechanism of metformin action
Gaochao Zhou,Robert W. Myers,Ying Li,Yuli Chen,Xiaolan Shen,Judy Fenyk-Melody,Margaret Wu,John Ventre,Thomas W. Doebber,Nobuharu Fujii,Nicolas Musi,Michael F. Hirshman,Laurie J. Goodyear,David E. Moller +13 more
TL;DR: It is reported that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed.
Journal ArticleDOI
The retinoblastoma protein and cell cycle control
TL;DR: The main role of pRB is to act as a signal transducer connecting the cell cycle clock with the transcriptional machinery, allowing the clock to control the expression of banks of genes that mediate advance of the cell through a critical phase of its growth cycle.
Journal ArticleDOI
Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase
Toshimasa Yamauchi,Junji Kamon,Yasuhiko Minokoshi,Yoichi M. Ito,Hironori Waki,S. Uchida,Shigeo Yamashita,Mitsuhiko Noda,Shunbun Kita,K Ueki,Koji Eto,Y. Akanuma,Philippe Froguel,Fabienne Foufelle,Pascal Ferré,David Carling,Shigeko Kimura,Ryozo Nagai,Barbara B. Kahn,Takashi Kadowaki +19 more
TL;DR: It is shown that phosphorylation and activation of the 5′-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full- lengths Ad in the liver, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK.