PMID- 27079798 OWN - NLM STAT- MEDLINE DCOM- 20170309 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Apr 15 TI - Lysine fatty acylation promotes lysosomal targeting of TNF-alpha. PG - 24371 LID - 10.1038/srep24371 [doi] LID - 24371 AB - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammation cytokine secreted by various cells. Understanding its secretive pathway is important to understand the biological functions of TNF-alpha and diseases associated with TNF-alpha. TNF-alpha is one of the first proteins known be modified by lysine fatty acylation (e.g. myristoylation). We previously demonstrated that SIRT6, a member of the mammalian sirtuin family of enzymes, can remove the fatty acyl modification on TNF-alpha and promote its secretion. However, the mechanistic details about how lysine fatty acylation regulates TNF-alpha secretion have been unknown. Here we present experimental data supporting that lysine fatty acylation promotes lysosomal targeting of TNF-alpha. The result is an important first step toward understanding the biological functions of lysine fatty acylation. FAU - Jiang, Hong AU - Jiang H AD - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA. FAU - Zhang, Xiaoyu AU - Zhang X AD - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA. FAU - Lin, Hening AU - Lin H AD - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA. AD - Howard Hughes Medical Institute, Cornell University, Ithaca, NY 14853, USA. LA - eng GR - GM086703/GM/NIGMS NIH HHS/United States GR - S10OD018516/OD/NIH HHS/United States GR - DK107868/DK/NIDDK NIH HHS/United States GR - Howard Hughes Medical Institute/United States GR - S10 OD018516/OD/NIH HHS/United States GR - R01 GM086703/GM/NIGMS NIH HHS/United States GR - R01 DK107868/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160415 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Tumor Necrosis Factor-alpha) RN - K3Z4F929H6 (Lysine) SB - IM MH - Acylation MH - Cell Line MH - Cytoplasmic Vesicles/metabolism MH - Humans MH - Lysine/*metabolism MH - Lysosomes/*metabolism MH - Organelles/metabolism MH - Protein Transport MH - Proteolysis MH - Tumor Necrosis Factor-alpha/*metabolism PMC - PMC4832147 EDAT- 2016/04/16 06:00 MHDA- 2017/03/10 06:00 PMCR- 2016/04/15 CRDT- 2016/04/16 06:00 PHST- 2015/12/07 00:00 [received] PHST- 2016/03/21 00:00 [accepted] PHST- 2016/04/16 06:00 [entrez] PHST- 2016/04/16 06:00 [pubmed] PHST- 2017/03/10 06:00 [medline] PHST- 2016/04/15 00:00 [pmc-release] AID - srep24371 [pii] AID - 10.1038/srep24371 [doi] PST - epublish SO - Sci Rep. 2016 Apr 15;6:24371. doi: 10.1038/srep24371.