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AMP-activated protein kinase: Structure, function, and role in pathological processes

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Abstract

Recently, AMP-activated protein kinase (AMPK) has emerged as a key regulator of energy balance at cellular and whole-body levels. Due to the involvement in multiple signaling pathways, AMPK efficiently controls ATP-consuming/ATP-generating processes to maintain energy homeostasis under stress conditions. Loss of the kinase activity or attenuation of its expression leads to a variety of metabolic disorders and increases cancer risk. In this review, we discuss recent findings on the structure of AMPK, its activation mechanisms, as well as the consequences of its targets in regulation of metabolism. Particular attention is given to low-molecular-weight compounds that activate or inhibit AMPK; the perspective of therapeutic use of such modulators in treatment of several common diseases is discussed.

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Abbreviations

ACC:

acetyl-CoA carboxylase

CaMKK:

Ca2+/calmodulin-dependent protein kinase kinase

CD36:

cluster of differentiation 36 fatty acid translocase

eEF2K:

eukaryotic elongation factor-2 kinase

eNOS:

endothelial nitric oxide synthase

FOXO3:

transcription factor of the forkhead family

GLUT1/GLUT4:

glucose transporter 1/glucose transporter 4

G6Pase:

glucose 6-phosphatase

GPAT:

glycerol phosphate acyl transferase

GS:

glycogen synthase

HDAC5:

histone deacetylase 5

HIF-1α:

hypoxia-inducible factor 1α

HKII:

hexokinase II

HMGR:

3-hydroxy-3-methyl-glutaryl-CoA reductase

HSL:

hormone-sensitive lipase

LKB1:

liver kinase B1

MO25:

mouse protein-25

mTOR:

mammalian target of rapamycin (kinase)

mTORC1:

mTOR kinase complex 1

NRF:

nuclear respiratory factor

6PFK2:

6-phosphofructo-2-kinase

PEPCK:

phosphoenolpyruvate carboxykinase

PGC-1α:

PPARγ coactivator 1α

PKA:

protein kinase A

PPAR:

peroxisome proliferator-activated receptor

Raptor:

regulatory-associated protein of mTOR

Rheb:

GTP-binding protein

SREBP-1c:

sterol regulatory element-binding protein 1c

STRAD:

STE20-related kinase adapter protein

TAK1:

TGF-β-activated kinase-1

TBC1D1/TBC1D4:

proteins of TBC1 domain family

TSC2:

tuberous sclerosis complex 2 (tuberin)

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Authors and Affiliations

  1. Saint Petersburg State Technological Institute, Technical University, Moskovsky pr. 26, 190013, St. Petersburg, Russia

    D. S. Novikova, A. V. Garabadzhiu, G. Melino, N. A. Barlev & V. G. Tribulovich

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  1. D. S. Novikova
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  2. A. V. Garabadzhiu
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  3. G. Melino
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  4. N. A. Barlev
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  5. V. G. Tribulovich
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Correspondence to D. S. Novikova.

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Published in Russian in Biokhimiya, 2015, Vol. 80, No. 2, pp. 163–183.

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Novikova, D.S., Garabadzhiu, A.V., Melino, G. et al. AMP-activated protein kinase: Structure, function, and role in pathological processes. Biochemistry Moscow 80, 127–144 (2015). https://doi.org/10.1134/S0006297915020017

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  • DOI: https://doi.org/10.1134/S0006297915020017

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