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. 2008 Aug 20;582(19):2843-9.
doi: 10.1016/j.febslet.2008.07.014. Epub 2008 Jul 15.

Protein Phosphatase 4 Negatively Regulates LPS Cascade by Inhibiting Ubiquitination of TRAF6

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Protein Phosphatase 4 Negatively Regulates LPS Cascade by Inhibiting Ubiquitination of TRAF6

Lu Chen et al. FEBS Lett. .
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Abstract

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.

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