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Cancer

Metabolic phosphatase moonlights for proteins

Nature Cell Biology volume 24, pages 1568–1570 (2022)Cite this article

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In tumours, cancer cells can overcome energy stress via differential regulation of non-canonical ‘moonlighting’ functions of metabolic enzymes. A study now shows that the metabolic phosphatase fructose-1,6-bisphosphatase 1 (FBP1) can act as a nuclear protein phosphatase and reveals how this process is inhibited in cancer cells.

Fructose-1,6-bisphosphatase (FBP) is a conserved metabolic enzyme that catalyses the rate-limiting hydrolysis of fructose-1,6-bisphosphate (F-1,6-BP) to fructose-6-phosphate (F-6-P) and inorganic phosphate during gluconeogenesis1. Vertebrates express two FBP isozymes: FBP1 in gluconeogenic organs and FBP2 ubiquitously in skeletal muscle and other tissues2. FBPases form homotetramers that switch between two conformational states, regulating their activity3.

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Fig. 1: Energy-stress-induced FBP1 signaling in normal hepatocytes and hepatocellular carcinoma cells.

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  1. Dartmouth Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

    Scott A. Gerber & Arminja N. Kettenbach

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  1. Scott A. Gerber
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  2. Arminja N. Kettenbach
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Correspondence to Arminja N. Kettenbach.

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Gerber, S.A., Kettenbach, A.N. Metabolic phosphatase moonlights for proteins. Nat Cell Biol 24, 1568–1570 (2022). https://doi.org/10.1038/s41556-022-00993-x

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