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Ubiquitin-proteasome signaling in lung injury

Published:April 23, 2018DOI:https://doi.org/10.1016/j.trsl.2018.04.003
      Cell homeostasis requires precise coordination of cellular proteins function. Ubiquitination is a post-translational modification that modulates protein half-life and function and is tightly regulated by ubiquitin E3 ligases and deubiquitinating enzymes. Lung injury can progress to acute respiratory distress syndrome that is characterized by an inflammatory response and disruption of the alveolocapillary barrier resulting in alveolar edema accumulation and hypoxemia. Ubiquitination plays an important role in the pathobiology of acute lung injury as it regulates the proteins modulating the alveolocapillary barrier and the inflammatory response. Better understanding of the signaling pathways regulated by ubiquitination may lead to novel therapeutic approaches by targeting specific elements of the ubiquitination pathways.

      Abbreviations:

      AJ (adherens junctions), ALI (acute lung injury), AMPK (adnosine monophosphate activated protein kinase), ARDS (acute respiratory distress syndrome), ATP (adenosine triphosphate), CFTR (cystic fibrosis transmembrane conductance regulator), cIAP (cellular inhibitor of apoptosis), CLR (cullin-RING ubiquitin ligase), ENaC (epithelial sodium channel), GSK3 (glycogen synthase kinase-3), HECT (homologous to the E6-AP C-terminus), HIF-1α (hypoxia-inducible factor 1α), HOIL-1L (Hemeoxidized IRP2 ubiquitin ligase 1L), HOIP (HOIL-1L interactin protein), IFN-γ (interferon gamma), IKK (IκB kinase), IL (interleukin), LUBAC (linear ubiquitination assembly complex), Met1 (N-terminal methionine), Nedd (neural precursor cell expressed developmentally downregulated protein), NEMO (NF-κB essential modulator), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), PKCζ (protein kinase C-zeta), RBR (ring in between ring), RING (really interesting new genes), RIPK1 (receptor-interacting serine-threonine kinase 1), SCF (skp1–Cullin–F-box protein), SHARPIN (SHANK-associated RH domain interacting protein), SUMO (small ubiquitin-like modifier), TAK1 (transforming growth factor-β-activated kinase 1), TJ (tight junctions), TNFα-R (tumor necrosis factor α-receptor), TNFR1-SC (TNFR1-signaling complex), TLR (toll like receptors), TRAF2 (TNFR-associated factor 2), Ub (ubiquitin), UBC13 (ubiquitin-conjugating13)
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