title: Lysine fatty acylation promotes lysosomal targeting of TNF-α.
abstract: Tumor necrosis factor-α (TNF-α) is a proinflammation cytokine secreted by various cells. Understanding its secretive pathway is important to understand the biological functions of TNF-α and diseases associated with TNF-α. TNF-α 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-α and promote its secretion. However, the mechanistic details about how lysine fatty acylation regulates TNF-α secretion have been unknown. Here we present experimental data supporting that lysine fatty acylation promotes lysosomal targeting of TNF-α. The result is an important first step toward understanding the biological functions of lysine fatty acylation.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.|Howard Hughes Medical Institute, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Hening
authors.initials: H
authors.lastname: Lin
mesh_terms: D000215:Acylation; D002460:Cell Line; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism; D021381:Protein Transport; D059748:Proteolysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008239:Lysine