We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1.
- Authors
Hong, Chang-Soo; Park, Mi-Ra; Sun, Eun-Gene; Choi, Wonyoung; Hwang, Jun-Eul; Bae, Woo-Kyun; Rhee, Joon Haeng; Cho, Sang-Hee; Chung, Ik-Joo
- Abstract
Galectin-3-binding protein (Gal-3BP) is a member of the family of scavenger receptor cysteine-rich (SRCR) domain-containing proteins, which are associated with the immune system. However, the functional roles and signaling mechanisms of Gal-3BP in host defense and the immune response remain largely unknown. Here, we identified cellular Gal-3BP as a negative regulator of NF-κB activation and proinflammatory cytokine production in lipopolysaccharide (LPS)-stimulated murine embryonic fibroblasts (MEFs). Furthermore, cellular Gal-3BP interacted with transforming growth factor β-activated kinase 1 (TAK1), a crucial mediator of NF-κB activation in response to cellular stress. Gal-3BP inhibited the phosphorylation of TAK1, leading to suppression of its kinase activity and reduced protein stability. In vivo we found that Lgals3BP deficiency in mice enhanced LPS-induced proinflammatory cytokine release and rendered mice more sensitive to LPS-induced endotoxin shock. Overall, these results suggest that Gal-3BP is a novel suppressor of TAK1-dependent NF-κB activation that may have potential in the prevention and treatment of inflammatory diseases.
- Subjects
PROTEIN stability; CARRIER proteins; NF-kappa B; CYTOKINES; IMMUNOREGULATION; INFLAMMATION; TRANSFORMING growth factors-beta; KINASES; CELLULAR signal transduction
- Publication
Frontiers in Immunology, 2019, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2019.01760