首页|TNF-?-induced E3 ligase, TRIM15 inhibits TNF-?-regulated NF-?B pathway by promoting turnover of K63 linked ubiquitination of TAK1
TNF-?-induced E3 ligase, TRIM15 inhibits TNF-?-regulated NF-?B pathway by promoting turnover of K63 linked ubiquitination of TAK1
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NSTL
Elsevier
Ubiquitin E3-ligases are recruited at different steps of TNF-alpha-induced NF-kappa B activation; however, their role in temporal regulation of the pathway remains elusive. The study systematically identified TRIMs as potential feedback regulators of the TNF-alpha-induced NF-kappa B pathway. We further observed that TRIM15 is "late" response TNF-alpha-induced gene and inhibits the TNF-alpha-induced NF-kappa B pathway in several human cell lines. TRIM15 promotes turnover of K63-linked ubiquitin chains in a PRY/SPRY domain-dependent manner. TRIM15 interacts with TAK1 and inhibits its K63-linked ubiquitination, thus NF-kappa B activity. Further, TRIM15 interacts with TRIM8 and inhibits cytosolic translocation to antagonize TRIM8 modualted NF-kappa B. TRIM8 and TRIM15 also show functionally inverse correlation in psoriasis condition. In conclusion, TRIM15 is TNF-alpha-induced late response gene and inhibits TNF-alpha induced NF-kappa B pathway hence a feedback modulator to keep the proinflammatory NF-kappa B pathway under control.
NSTL
Elsevier
