STING induces HOIP-mediated synthesis of M1 ubiquitin chains to stimulate NF-κB signaling
2024

How STING Activates Immune Signaling

publication 10 minutes Evidence: high

Author Information

Author(s): Tara D Fischer, Eric N Bunker, Peng-Peng Zhu, François Le Guerroué, Mahan Hadjian, Eunice Dominguez-Martin, Francesco Scavone, Robert Cohen, Tingting Yao, Yan Wang, Achim Werner, Richard J Youle

Primary Institution: National Institutes of Health

Hypothesis

How does STING activation lead to NF-κB signaling through ubiquitin chain formation?

Conclusion

The study shows that STING activation induces the formation of M1-linked ubiquitin chains, which are crucial for stimulating NF-κB signaling.

Supporting Evidence

  • STING activation leads to the recruitment of the E3 ligase HOIP.
  • HOIP is essential for the formation of M1-linked ubiquitin chains.
  • M1-linked ubiquitin chains stimulate NF-κB signaling.
  • Loss of HOIP reduces STING-induced NF-κB signaling.
  • LC3B lipidation is not required for M1-linked ubiquitin chain formation.

Takeaway

When a part of our immune system called STING gets activated, it helps make special chains of proteins that signal our body to fight infections.

Methodology

The study used immunostaining, immunoblotting, and mass spectrometry to analyze ubiquitin chain formation in response to STING activation.

Limitations

The study does not explore the long-term effects of STING activation on immune signaling.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1038/s44318-024-00291-2

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