Protein phosphatase 4 negatively regulates LPS cascade by inhibiting ubiquitination of TRAF6.

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, PR China.
TRAF6 is an E3 ubiquitin ligase that transduces signals from members of the TLR/IL-1R family. Multiple molecules have been found to associate with TRAF6 and exert their functions in this pathway. Herein, by yeast two-hybrid screen using TRAF6 as bait, we identified PP4 as a potential TRAF6-interacting protein. PP4 physically interacted with TRAF6 and was recruited to TLR4 complex upon LPS stimulation. PP4 negatively regulated LPS-induced and TRAF6-mediated NF-kappaB activation by inhibiting the ubiquitination of TRAF6. LPS stimulation also induced the expression of PP4. Taken together, our findings suggest that PP4 is a negative feedback regulator of LPS/TLR4 pathway.
Mesh Terms:
Animals, Cell Line, Feedback, Physiological, Humans, Lipopolysaccharides, Mice, NF-kappa B, Phosphoprotein Phosphatases, TNF Receptor-Associated Factor 6, Toll-Like Receptor 4, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases, Ubiquitination
FEBS Lett. Aug. 20, 2008; 582(19);2843-9 [PUBMED:18634786]
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