| First Author | Sun J | Year | 2022 |
| Journal | Front Cell Dev Biol | Volume | 10 |
| Pages | 877039 | PubMed ID | 35433693 |
| Mgi Jnum | J:323858 | Mgi Id | MGI:7263594 |
| Doi | 10.3389/fcell.2022.877039 | Citation | Sun J, et al. (2022) KIZ/GM114 Balances the NF-kB Signaling by Antagonizing the Association of TRAF2/6 With Their Upstream Adaptors. Front Cell Dev Biol 10:877039 |
| abstractText | NF-kappaB signaling is a pivotal regulator of the inflammatory response and it must be tightly controlled to avoid an excessive inflammatory response that may lead to human chronic inflammatory and autoimmune diseases. Thus, how NF-kappaB signaling is precisely controlled is a long-standing question in the field. TRAF family proteins function as key adaptors to mediate NF-kappaB signaling induced by various receptors. Here, we characterize KIZ/GM114 as a negative regulator balancing the NF-kappaB signaling. Mechanistically, KIZ/GM114 binds TRAF6/2 by targeting the TRAF domains to antagonize the TRAF6-IRAK1 association or the TRAF2-TRADD association, consequently reducing the IL-1beta/LPS/TNFalpha-induced NF-kappaB activation. Importantly, upon dextran sulfate sodium treatment, Gm114 deficiency induces a stronger inflammatory response, more severe acute colitis and lower survival rate in mice compared with control mice. Collectively, our study not only identifies KIZ/GM114 as a negative regulator to balance the NF-kappaB signaling, but it also implies a new strategy for limiting excessive inflammatory response. |
