TRIM56 positively regulates TNFa-induced NF-?B signaling by enhancing the ubiquitination of TAK1

Nuclear factor-kappa B (NF-kappa B) signaling participates in many biologic processes including immunity, inflammation, and cancer. Here we reported that tripartite motif-containing protein 56 (TRIM56), an E3 ligase enzyme, participated in TNF alpha-induced NF-kappa B signaling by interacting with TAK1. Overexpression of TRIM56 potentiated the activation of TNF alpha-induced NF-kappa B signaling, whereas knockdown of TRIM56 had an opposite effect. TRIM56 enhanced the ubiquitination of TAK1, specifically enhanced the M1-linked polyubiquitin chains to TAK1, leading to the tight interactions of the TAK1-IKK alpha complex. Consequently, the stimulation of TNFa and TRIM56 strengthened the interaction with TAK1. Furthermore, we found that the C terminal (CT) domain was the binding region of TRIM56, and the RING domain of TRIM56 was the E3 enzyme activity region which was important to the ubiquitination of TAK1. Together, these results reveal that TRIM56 positively regulates TNF alpha-induced NF-kappa B signaling by heightening the ubiquitination of TAK1 and provide new insight into the complicated mechanisms of the inflammatory and immune response.

Automated summary

TRIM56 plays a positive role in TNF alpha-induced NF-kappa B signaling by enhancing the ubiquitination of TAK1, providing new insights into the complex mechanisms of inflammation and immune response.