CALML6 Controls TAK1 Ubiquitination and Confers Protection against Acute Inflammation.
Proper regulation of innate immune response is important for individual health. The NF-?B signaling pathway plays crucial roles in innate immunity and inflammation, and its aberrant activation is implicated in diverse diseases and disorders. In this study, we report that calmodulin-like 6 (CALML6), a member of the EF-hand protein family, ... is a negative regulator of the NF-?B signaling pathway. CALML6 attenuated TNF-stimulated phosphorylation of proteins downstream of TGF-?-activated kinase 1 (TAK1) and inhibited TAK1-induced NF-?B activation. Further studies showed that CALML6 interacted with TAK1 and recruited the deubiquitylating enzyme cylindromatosis to repress the K63-linked polyubiquitination of TAK1. CALML6 transgenic mice had higher tolerances to lethal LPS treatment in vivo. These findings suggest that CALML6 is a negative regulator of the NF-?B signaling pathway, which is important for maintaining the balance of the innate immune response.
Mesh Terms:
Animals, Calcium-Binding Proteins, Calmodulin, Disease Models, Animal, Homeostasis, Humans, Immunity, Innate, Inflammation, MAP Kinase Kinase Kinases, Mice, Mice, Transgenic, NF-kappa B, Phosphorylation, Protein Binding, Sepsis, Signal Transduction, Transforming Growth Factor beta, Tumor Necrosis Factor-alpha, Ubiquitination
Animals, Calcium-Binding Proteins, Calmodulin, Disease Models, Animal, Homeostasis, Humans, Immunity, Innate, Inflammation, MAP Kinase Kinase Kinases, Mice, Mice, Transgenic, NF-kappa B, Phosphorylation, Protein Binding, Sepsis, Signal Transduction, Transforming Growth Factor beta, Tumor Necrosis Factor-alpha, Ubiquitination
J Immunol
Date: Dec. 01, 2019
PubMed ID: 32303555
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