MEK1-dependent MondoA phosphorylation regulates glucose uptake in response to ketone bodies in colorectal cancer cells.

ABSTRACT: The Mondo family transcription factor MondoA plays a pivotal role in sensing metabolites, such as glucose, glutamine, and lactic acid, to regulate glucose metabolism and cell proliferation. Ketone bodies are important signals for reducing glucose uptake. However, it is unclear whether MondoA functions in ketone body-regulated glucose transport. Here we reported that ketone bodies promoted MondoA nuclear translocation and binding to the promoter of its target gene TXNIP. Ketone bodies reduced glucose uptake, increased apoptosis and decreased proliferation of colorectal cancer cells, which was impeded by MondoA knockdown. Moreover, we identified MEK1 as a novel component of the MondoA protein complex using a proteomic approach. Mechanistically, MEK1 interacted with MondoA and enhanced tyrosi

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC9986092 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature