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Fbxo7 promotes Cdk6 activity to inhibit PFKP and glycolysis in T cells

Rebecca Harris1, Ming Yang2, Christina Schmidt2

  • 1Department of Pathology, University of Cambridge, Cambridge, UK.

The Journal of Cell Biology
|June 7, 2022
PubMed

Insights

Fbxo7 protein regulates T cell metabolism by controlling glycolysis via Cdk6 activation. Reduced Fbxo7 increases glycolysis but decreases T cell viability and activation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Immunology

Background:

  • Fbxo7 protein is implicated in cancer and Parkinson's disease.
  • Fbxo7 influences SCF-type ubiquitin ligase activity and Cdk6 activation.
  • PFKP, a key enzyme in glycolysis, is identified as a Cdk6 substrate.

Purpose of the Study:

  • Investigate the molecular interplay between Fbxo7, Cdk6, and PFKP.
  • Determine Fbxo7's impact on T cell metabolism, viability, and activation.
  • Elucidate Fbxo7's role in regulating glycolysis and cellular processes.

Main Methods:

  • Protein interaction and activity assays to study Fbxo7, Cdk6, and PFKP.
  • Cellular assays to assess T cell metabolism, viability, and activation.
  • Metabolomic analysis of Fbxo7-deficient T cells.

Main Results:

  • Fbxo7 modulates PFKP phosphorylation in a Cdk6-dependent manner.
  • Fbxo7 deficiency leads to reduced Cdk6 activity and increased glycolysis in T cells.
  • Reduced Fbxo7 expression impairs T cell viability and activation despite elevated glycolytic flux.

Conclusions:

  • Fbxo7 regulates T cell glycolysis and metabolism through Cdk6-dependent PFKP phosphorylation.
  • Fbxo7 plays a critical role in maintaining T cell function and viability.
  • Fbxo7 expression is responsive to glucose levels, suggesting a role in metabolic adaptation.

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