Detection of nuclear STING in cultured human cells and in the normal and cancer tissues

Stimulator of interferon genes (STING) mediates responses to pathogen DNA and to breakdown intermediates of intracellular mitochondrial and genomic DNA. STING is located predominantly on the endoplasmic reticulum; however, a fraction of the protein is found in the inner nuclear membrane. Though STING loss affects processes such as DNA repair and replication stress response, the role of nuclear STING is not understood. We established a proximity ligation assay-based approach to measure nuclear STING based on its proximity to the nuclear lamina. STING nuclear distribution was found to be affected by the expression of a mutant form of lamin A, progerin, and did not require STING C-terminal domain. STING was detected in micronuclei where it promoted the accumulation of cGAS in a manner dependent on oligomerization and activation. Nuclear STING was also found in human formalin-fixed and paraffin-embedded (FFPE) samples of normal and cancerous female reproductive and lung tissues, where its levels were overall proportionate to the total cellular levels of STING.