TIFA: a signaling hub linking inflammation, innate immunity, and human disease
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By
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Yizhuo Fu
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Yiting Zhan
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Limei Li
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Wenzhi Shen
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Chunlei Guo
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June 8, 2026
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Objective:
To summarize the structural basis of TIFA activation, its signaling mechanisms, and its roles in human disease.
Key Findings:
- TIFA facilitates the oligomerization and ubiquitination of TRAF6, activating NF-κB-dependent inflammatory pathways.
- The ALPK1-TIFA signaling pathway links microbial metabolite sensing to immune responses.
- TIFA exhibits context-dependent dual roles, acting as an oncogenic factor in some contexts and a tumor suppressor in others.
Interpretation:
TIFA plays a role in innate immune signaling and inflammation, with implications for various human diseases.
Limitations:
- The review does not provide experimental data but summarizes existing literature.
- Context-dependent roles of TIFA may complicate therapeutic targeting.
Conclusion:
TIFA's role as a signaling hub in inflammation and immunity is highlighted in the review.
