IRF3 and cancer: For example, TG2 has been shown to negatively regulate the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway by impairing interferon regulatory factor 3 (IRF3) phosphorylation independent of its transamidase activity in human melanoma cells, suggesting a role of TG2 in reducing type I interferon (IFNI) production after DNA damage to limit the immune system response in cancer cells [37].