Open AccessA newly discovered role of metabolic enzyme PCK1 as a protein kinase to promote cancer lipogenesis
Author(s) -
Jiang Hongfei,
Zhu Lei,
Xu Daqian,
Lu Zhimin
Publication year - 2020
Publication title -
cancer communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.119
H-Index - 53
ISSN - 2523-3548
DOI - 10.1002/cac2.12084
Subject(s) - lipogenesis , sterol regulatory element binding protein , oxysterol , protein kinase a , chemistry , microbiology and biotechnology , biochemistry , phosphorylation , biology , lipid metabolism , sterol , cholesterol
Highly active lipogenesis is essential for rapid tumor growth. Sterol regulatory element‐binding protein (SREBP) is a key transcriptional factor for lipogenesis and activated by reduced sterol and oxysterol levels. However, the mechanism by which cancer cells activate SREBP without altering these sterol/oxysterol levels remains elusive. In one of our recent studies published in Nature entitled “The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis”, we demonstrated that activated AKT‐mediated phosphoenolpyruvate carboxykinase 1 (PCK1) S90 phosphorylation reduces the gluconeogenic activity of PCK1 and triggers its translocation to the endoplasmic reticulum (ER), where PCK1 acts as a protein kinase and uses GTP, rather than ATP, as a phosphate donor to phosphorylate Insig1/2 thereby reducing oxysterol's binding to Insig1/2 and activating SREBP‐mediated lipogenesis for tumor growth. These findings elucidate a coordinated regulation between gluconeogenesis and lipogenesis and uncover a critical role of the protein kinase activity of PCK1 in SREBP‐dependent lipid synthesis.