{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wen Z"],"funding":["BLRD VA","NIA NIH HHS","NIAID NIH HHS","NHLBI NIH HHS","NIAMS NIH HHS"],"pagination":["313-325"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6396296"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(3)"],"pubmed_abstract":["N-myristoyltransferase (NMT) attaches the fatty acid myristate to the N-terminal glycine of proteins to sort them into soluble and membrane-bound fractions. Function of the energy-sensing AMP-activated protein kinase, AMPK, is myristoylation dependent. In rheumatoid arthritis (RA), pathogenic T cells shift glucose away from adenosine tri-phosphate production toward synthetic and proliferative programs, promoting proliferation, cytokine production, and tissue invasion. We found that RA T cells had a defect in NMT1 function, which prevented AMPK activation and enabled unopposed mTORC1 signaling. Lack of the myristate lipid tail disrupted the lysosomal translocation and activation of AMPK. Instead, myristoylation-incompetent RA T cells hyperactivated the mTORC1 pathway and differentiated into pro-inflammatory TH1 and TH17 helper T cells. In vivo, NMT1 loss caused robust synovial tissue inflammation, whereas forced NMT1 overexpression rescued AMPK activation and suppressed synovitis. Thus, NMT1 has tissue-protective functions by facilitating lysosomal recruitment of AMPK and dampening mTORC1 signaling."],"journal":["Nature immunology"],"pubmed_title":["N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation."],"pmcid":["PMC6396296"],"funding_grant_id":["R01 HL142068","R01 AG045779","U19 AI057266","R01 AR042527","R01 HL117913","I01 BX001669","R01 AI108891","P01 HL129941","R01 AI108906"],"pubmed_authors":["Yang Z","Li Y","Tian L","Weyand CM","Wen Z","Wu B","Shen Y","Shoor S","Jin K","Roche NE","Goronzy JJ"],"additional_accession":[]},"is_claimable":false,"name":"N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation.","description":"N-myristoyltransferase (NMT) attaches the fatty acid myristate to the N-terminal glycine of proteins to sort them into soluble and membrane-bound fractions. Function of the energy-sensing AMP-activated protein kinase, AMPK, is myristoylation dependent. In rheumatoid arthritis (RA), pathogenic T cells shift glucose away from adenosine tri-phosphate production toward synthetic and proliferative programs, promoting proliferation, cytokine production, and tissue invasion. We found that RA T cells had a defect in NMT1 function, which prevented AMPK activation and enabled unopposed mTORC1 signaling. Lack of the myristate lipid tail disrupted the lysosomal translocation and activation of AMPK. Instead, myristoylation-incompetent RA T cells hyperactivated the mTORC1 pathway and differentiated into pro-inflammatory TH1 and TH17 helper T cells. In vivo, NMT1 loss caused robust synovial tissue inflammation, whereas forced NMT1 overexpression rescued AMPK activation and suppressed synovitis. Thus, NMT1 has tissue-protective functions by facilitating lysosomal recruitment of AMPK and dampening mTORC1 signaling.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Mar","modification":"2024-11-20T15:32:19.015Z","creation":"2019-08-07T07:03:22Z"},"accession":"S-EPMC6396296","cross_references":{"pubmed":["30718913"],"doi":["10.1038/s41590-018-0296-7"]}}