Kiz, also known as GM114, is a negative regulator that balances the NF-κB signaling pathway. NF-κB signaling is crucial for the inflammatory response, and tight control of this pathway is essential to prevent excessive inflammation-related chronic and autoimmune diseases. Kiz functions by binding to TRAF6/2 through targeting their TRAF domains, antagonizing the association between TRAF6-IRAK1 or TRAF2-TRADD, thus reducing IL-1β/LPS/TNFα-induced NF-κB activation [1].

In a dextran sulfate sodium-treated mouse model, Gm114 deficiency led to a stronger inflammatory response, more severe acute colitis, and a lower survival rate compared to control mice. This indicates that Kiz plays a significant role in limiting excessive inflammatory responses in vivo [1].

In conclusion, Kiz is a key negative regulator of the NF-κB signaling pathway, and its deficiency in mouse models reveals its importance in maintaining appropriate levels of the inflammatory response, highlighting its potential as a target for treating inflammatory-related diseases.

References:

1. Sun, Jiawei, Yang, Qili, Liu, Enping, Chen, Dahua, Sun, Qinmiao. 2022. KIZ/GM114 Balances the NF-ĸB Signaling by Antagonizing the Association of TRAF2/6 With Their Upstream Adaptors. In Frontiers in cell and developmental biology, 10, 877039. doi:10.3389/fcell.2022.877039. https://pubmed.ncbi.nlm.nih.gov/35433693/