PMID- 26369908 OWN - NLM STAT- MEDLINE DCOM- 20160909 LR - 20181113 IS - 1460-2423 (Electronic) IS - 0959-6658 (Print) IS - 0959-6658 (Linking) VI - 26 IP - 1 DP - 2016 Jan TI - Identification and biological consequences of the O-GlcNAc modification of the human innate immune receptor, Nod2. PG - 13-8 LID - 10.1093/glycob/cwv076 [doi] AB - Nucleotide-binding oligomerization domain 2 (Nod2) is an intracellular receptor that can sense the bacterial peptidoglycan component, muramyl dipeptide. Upon activation, Nod2 induces the production of various inflammatory molecules such as cytokines and chemokines. Genetic linkage analysis identified and revealed three major mutations in Nod2 that are associated with the development of Crohn's disease. The objective of this study is to further characterize this protein by determining whether Nod2 is posttranslationally modified by O-N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation is one type of posttranslational modification in which the O-GlcNAc transferase transfers GlcNAc from UDP-GlcNAc to selected serine and threonine residues of intracellular proteins. We found that wild-type Nod2 and a Nod2 Crohn's-associated variant are O-GlcNAcylated and this modification affects Nod2's ability to signal via the nuclear factor kappa B pathway. CI - (c) The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Hou, Ching-Wen AU - Hou CW AD - Department of Chemistry and Biochemistry. FAU - Mohanan, Vishnu AU - Mohanan V AD - Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA. FAU - Zachara, Natasha E AU - Zachara NE AD - Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. FAU - Grimes, Catherine Leimkuhler AU - Grimes CL AD - Department of Chemistry and Biochemistry Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA cgrimes@udel.edu. LA - eng GR - P01 HL107153/HL/NHLBI NIH HHS/United States GR - P30 DK079637/DK/NIDDK NIH HHS/United States GR - P01HL107153/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150914 PL - England TA - Glycobiology JT - Glycobiology JID - 9104124 RN - 0 (NF-kappa B) RN - 0 (NOD2 protein, human) RN - 0 (Nod2 Signaling Adaptor Protein) RN - V956696549 (Acetylglucosamine) SB - IM MH - Acetylglucosamine/*metabolism MH - Glycosylation MH - HCT116 Cells MH - HEK293 Cells MH - Humans MH - Mutation MH - NF-kappa B/metabolism MH - Nod2 Signaling Adaptor Protein/genetics/*metabolism MH - *Protein Processing, Post-Translational PMC - PMC4672147 OTO - NOTNLM OT - Crohn's disease OT - NF-kappaB OT - Nod2 OT - O-GlcNAcylation OT - OGT EDAT- 2015/09/16 06:00 MHDA- 2016/09/10 06:00 PMCR- 2017/01/01 CRDT- 2015/09/16 06:00 PHST- 2015/05/14 00:00 [received] PHST- 2015/09/04 00:00 [accepted] PHST- 2015/09/16 06:00 [entrez] PHST- 2015/09/16 06:00 [pubmed] PHST- 2016/09/10 06:00 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - cwv076 [pii] AID - 10.1093/glycob/cwv076 [doi] PST - ppublish SO - Glycobiology. 2016 Jan;26(1):13-8. doi: 10.1093/glycob/cwv076. Epub 2015 Sep 14.