O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase.

Autor: Fan Q; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 1046 Blindern, 0317 Oslo, Norway., Moen A; Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 1041 Blindern, 0317 Oslo, Norway., Anonsen JH; Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 1041 Blindern, 0317 Oslo, Norway; CIME, Center for Integrative Microbial Evolution, University of Oslo, 1041 Blindern, 0317 Oslo, Norway., Bindesbøll C; Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 1046 Blindern, 0317 Oslo, Norway., Sæther T; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 1046 Blindern, 0317 Oslo, Norway., Carlson CR; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway., Grønning-Wang LM; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 1046 Blindern, 0317 Oslo, Norway. Electronic address: lmgronningwang@gmail.com.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2018 May 05; Vol. 499 (2), pp. 354-360. Date of Electronic Publication: 2018 Mar 26.
DOI: 10.1016/j.bbrc.2018.03.164
Abstrakt: The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses. We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity. Moreover, we showed that LXRα associates with O-GlcNAc transferase (OGT) in vitro and in vivo in mouse liver. In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20 LWKPGAQDASSQAQGGSSCILRE 42 . However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro. Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion. Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain. We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain. Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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