Liu E, Sun J, Yang J, Li L, Yang Q, Zeng J, Zhang J, Chen D, Sun Q

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a RING domain ubiquitin ligase that plays an important role in nuclear factor-?B (NF-?B) signaling by regulating activation of the TAK1 and IKK complexes. However, the molecular mechanisms that regulate TRAF6 E3 activity remain unclear. Here, we found that ZDHHC11, a member ...

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of the DHHC palmitoyl transferase family, functions as a positive modulator in NF-?B signaling. ZDHHC11 overexpression activated NF-?B, whereas ZDHHC11 deficiency impaired NF-?B activity stimulated by IL-1?, LPS, and DNA virus infection. Furthermore, Zdhhc11 knockout mice had a lower level of serum IL6 upon treatment with LPS and D-galactosamine or HSV-1 infection than control mice. Mechanistically, ZDHHC11 interacted with TRAF6 and then enhanced TRAF6 oligomerization, which increased E3 activity of TRAF6 for synthesis of K63-linked ubiquitination chains. Collectively, our study indicates that ZDHHC11 positively regulates NF-?B signaling by promoting TRAF6 oligomerization and ligase activity, subsequently activating TAK1 and IKK complexes.

Date: Sep. 08, 2021

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