The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation. (https://pubmed.ncbi.nlm.nih.gov/38418882/)

These scientists wanted to understand how a protein called cGAS is controlled inside the cell. cGAS is like a security guard that helps protect the cell from harmful things like infections and diseases. They found that cGAS can become too active and cause problems if not regulated properly.

To figure out how cGAS is controlled, the scientists looked at how another group of proteins, called the ubiquitin proteasomal system (UPS), work together to break down cGAS in the cell's nucleus. They discovered a specific protein called SPSB3 that helps tag cGAS for destruction by the UPS.

By studying the structure of cGAS and SPSB3 together, the scientists found a special code at the end of cGAS that tells SPSB3 to target and break down cGAS. When they interfered with this process, they noticed that the cell's defense system became stronger against certain viruses.

Overall, this study showed how the cell controls cGAS to prevent it from becoming too active and causing problems. This new knowledge could help scientists develop treatments for diseases caused by cGAS dysfunction in the future.

Xu P., Liu Y., Liu C., Guey B., Li L., Melenec P., Ricci J., Ablasser A. The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation. Nature. 2024 Feb 28. doi: 10.1038/s41586-024-07112-w.