cGAS-STING Cytosolic DNA Sensing Project
Overview
The cGAS-STING pathway is a critical innate immune signaling system that detects cytosolic DNA (from pathogens, damaged mitochondria, or genomic instability) and triggers type I interferon responses. Many regulators and disease connections have been discovered 2020+.
Model Species
Primary: Homo sapiens (human)
- Cancer immunotherapy relevance
- Autoimmune disease connections
Core Pathway Architecture
1. DNA Sensing
- CGAS (MB21D1) - Cyclic GMP-AMP synthase, DNA sensor
- IFI16 - Alternative DNA sensor
2. Second Messenger
- cGAMP - 2'3'-cyclic GMP-AMP (product of cGAS)
- ENPP1 - Degrades extracellular cGAMP
3. Signal Transduction
- STING1 (TMEM173) - ER-resident adaptor
- TBK1 - Tank-binding kinase 1
- IRF3 - Interferon regulatory factor 3
- NFKB1 - NF-κB pathway
4. Negative Regulators
- TREX1 - Cytosolic exonuclease (prevents self-DNA sensing)
- SAMHD1 - dNTPase, HIV restriction factor
- Various ubiquitin regulators
5. Downstream Effectors
- Type I interferons - IFNA, IFNB
- Inflammatory cytokines
Candidate Genes (~15)
| Gene | UniProt | Function |
|---|---|---|
| CGAS | Q8N884 | DNA sensor |
| STING1 | Q86WV6 | Adaptor protein |
| TBK1 | Q9UHD2 | Kinase |
| IRF3 | Q14653 | Transcription factor |
| TREX1 | Q9NSU2 | Negative regulator |
| ENPP1 | P22413 | cGAMP hydrolase |
| IFI16 | Q16666 | DNA sensor |
| SAMHD1 | Q9Y3Z3 | dNTPase |
| IRF7 | Q92985 | Transcription factor |
| IFNB1 | P01574 | Type I interferon |
Key Recent Discoveries (2020+)
- STING trafficking and degradation mechanisms
- cGAMP transfer between cells
- STING agonists in cancer therapy
- Mitochondrial DNA sensing in aging
- STING in senescence
Disease Relevance
- Cancer immunotherapy (STING agonists)
- Autoimmunity (AGS, SAVI, lupus)
- Viral infection
- Aging/senescence
Project Status
- [ ] Stub - needs gene folder setup