Researchers have identified the protein MYO1F as a key regulator of T-cell metabolism, with implications for immune responses, cancer, and autoimmune diseases. The study reveals that MYO1F is essential for T-cell activation after T-cell receptor (TCR) stimulation. Mice lacking Myo1f in T cells exhibited increased tumour growth and reduced severity of autoimmune inflammation, highlighting its importance in T-cell function.
The researchers found that MYO1F is phosphorylated by the kinase LCK at specific tyrosine residues after TCR stimulation. This phosphorylation drives the acetylation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key glycolytic enzyme, at critical lysine sites. GAPDH acetylation, mediated by the enzyme α-TAT1, activates glycolysis, enabling T cells to perform their effector functions.
The study also uncovered a link between MYO1F and peripheral T-cell lymphoma (PTCL). A fusion protein, VAV1-MYO1F, found in PTCL patients, induces excessive acetylation and overactivation of GAPDH, driving abnormal glycolysis and T-cell proliferation. Inhibition of GAPDH activity in mice expressing the VAV1-MYO1F fusion protein reduced tumour growth and extended survival. Hyperacetylated GAPDH was also confirmed in human PTCL samples containing the VAV1-MYO1F gene fusion.
These findings suggest that targeting GAPDH acetylation or its downstream effects could offer novel therapeutic options for PTCL and other diseases involving dysregulated T-cell metabolism. This research represents a significant step forward in understanding T-cell biology and developing treatments for cancer and immune-mediated disorders.
Helena Bradbury, EMJ
Reference
Cui Z et al. MYO1F regulates T-cell activation and glycolytic metabolism by promoting the acetylation of GAPDH. Cellular & Molecular Immunology. 2024. doi: 10.1038/s41423-024-01247-6.
