Adenylate Kinase and Metabolic Signaling in Cancer Cells

Frontiers in Oncology
Aleksandr KlepininPetras Dzeja

Abstract

A hallmark of cancer cells is the ability to rewire their bioenergetics and metabolic signaling circuits to fuel their uncontrolled proliferation and metastasis. Adenylate kinase (AK) is the critical enzyme in the metabolic monitoring of cellular adenine nucleotide homeostasis. It also directs AK→ AMP→ AMPK signaling controlling cell cycle and proliferation, and ATP energy transfer from mitochondria to distribute energy among cellular processes. The significance of AK isoform network in the regulation of a variety of cellular processes, which include cell differentiation and motility, is rapidly growing. Adenylate kinase 2 (AK2) isoform, localized in intermembrane and intra-cristae space, is vital for mitochondria nucleotide exchange and ATP export. AK2 deficiency disrupts cell energetics, causes severe human diseases, and is embryonically lethal in mice, signifying the importance of catalyzed phosphotransfer in cellular energetics. Suppression of AK phosphotransfer and AMP generation in cancer cells and consequently signaling through AMPK could be an important factor in the initiation of cancerous transformation, unleashing uncontrolled cell cycle and growth. Evidence also builds up that shift in AK isoforms is used later by c...Continue Reading

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Citations

Mar 20, 2021·Analytica Chimica Acta·Cemil Can EylemEmirhan Nemutlu
Apr 30, 2021·Journal of the American Chemical Society·Justina ŠileikytėMichael S Cohen
Jun 3, 2021·International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ernährungsforschung. Journal international de vitaminologie et de nutrition·David StuckiWilhelm Stahl
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Sep 6, 2021·Biological Trace Element Research·José Cavalcante Souza VieiraPedro de Magalhães Padilha
Jan 5, 2022·PloS One·Michiyo MaruyamaTakashi Yoshimura

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Methods Mentioned

BETA
nucleotide exchange
NMR

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