title: Regulation of inflammation by DAPK.
abstract: Death-associated protein kinase (DAPK) is a tumor suppressor and negatively regulates several activation signals. Consistent with its potential anti-inflammatory activity, DAPK promotes the formation of IFN-γ-activated inhibitor of translation (GAIT) complex that suppresses the translation of selected inflammatory genes. DAPK has been found to inhibit tumor necrosis factor-α (TNF-α)- or lipopolysaccharides (LPS)-induced NF-κB activation and pro-inflammatory cytokine expression. Inflammation is always associated with T cell activation, while DAPK attenuates T cell activation by a selective suppression in T cell receptor-triggered NF-κB activation. Recent studies, however, also reveal a contribution of DAPK to pro-inflammatory processes. DAPK is shown to mediate pro-inflammatory signaling downstream of TNF-α, LPS, IL-17, or IL-32. In addition, DAPK is required for the full formation of NLRP3 inflammasome, essential for the generation of IL-1β and IL-18. These results suggest the complicated role of DAPK in the regulation of inflammation that is likely dependent on cell types and environmental cues.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan, ROC, mblai@gate.sinica.edu.tw.
authors.forename: Ming-Zong
authors.initials: MZ
authors.lastname: Lai
authors.forename: Ruey-Hwa
authors.initials: RH
authors.lastname: Chen
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D064550:Death-Associated Protein Kinases / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D064550:Death-Associated Protein Kinases