A newly discovered role of metabolic enzyme PCK1 as a protein kinase to promote cancer lipogenesis.

Abstract

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.

• Authors: Hongfei Jiang, Lei Zhu, Daqian Xu, Zhimin Lu
• Journal: Cancer communications (London, England) (Cancer Commun (Lond)) Vol. 40 Issue 9 Pg. 389-394 (09 2020) ISSN: 2523-3548 [Electronic] United States
• PMID: 32809272 (Publication Type: Editorial)
• Copyright: © 2020 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.

Chemical References

• Intracellular Signaling Peptides and Proteins
• SREBF1 protein, human
• Sterol Regulatory Element Binding Protein 1
• Protein Kinases
• PCK1 protein, human
• Phosphoenolpyruvate Carboxykinase (GTP)

Topics

• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• Lipogenesis
• Neoplasms (pathology)
• Phosphoenolpyruvate Carboxykinase (GTP) (genetics, metabolism)
• Phosphorylation
• Protein Kinases
• Sterol Regulatory Element Binding Protein 1 (metabolism)