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Abstract
Background: O-GlcNAcylation is a posttranslational modification associated with various physiological and pathophysiological processes including diabetes, cancer, neurodegeneration and inflammation. However, the biological mechanisms underlying the role of specific O-GlcNAc sites and their link to phenotypes remain largely unexplored due to lack of suitable in vivo models. TGF-β activated kinase-1 binding protein-1 (TAB1) is a scaffolding protein required for TGF-β activated kinase-1 (TAK1) mediated signalling. A single O-GlcNAc site has been identified on human TAB1 that modulates TAK1-mediated cytokine release in cells.
Methods: Here, we report the generation of the Tab1 S393A mouse model using a constitutive knock-in strategy. The Tab1 S393A mice carry a Ser393Ala (S393A) mutation that leads to loss of O-GlcNAcylation site on TAB1.
Results: We did not observe any obvious phenotype in Tab1 S393A mice. Loss of O-GlcNAcylation on TAB1 has no consequences on TAB1 protein level or on TAB1-TAK1 interaction.
Conclusions: The homozygous Tab1 S393A mice are viable and develop with no obvious abnormalities, providing a powerful tool to further investigate the role of O-GlcNAc on TAB1 in the inflammatory response in the context of a whole organism.
Original language | English |
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Article number | 128 |
Number of pages | 16 |
Journal | Wellcome Open Research |
Volume | 4 |
DOIs | |
Publication status | Published - 27 Aug 2019 |
Keywords
- O-GlcNAcylation
- TAB1
- TAK1
- signalling
- inflammation
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- 1 Finished
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Molecular Mechanisms of O-GICNAC Signalling (Investigator award)
van Aalten, D. (Investigator)
1/03/16 → 28/02/22
Project: Research