Pyruvate is a natural suppressor of interferon signaling by inducing STAT1 protein pyruvylation

Glycolysis is a central metabolic pathway that converts glucose into pyruvate. Although pyruvate has been well documented to be a key and terminal metabolite of glycolysis with both energetic and biosynthetic roles, its non-metabolic functions remain unexplored. Here, we report a pyruvate-mediated protein post-translational modification (PTM), protein pyruvylation. We reveal that high glucose-upregulated glycolysis promotes signal transducer and activator of transcription 1 (STAT1) pyruvylation at Lys201 (K201), which blocks STAT1 and signal transducer and activator of transcription 2 (STAT2) interaction, thus suppressing type I interferon (IFN-I) signaling and antiviral immune activity. Consequently,…

• NN
  National Natural Science Foundation of China
• CP
  China Postdoctoral Science Foundation