title: The emerging role of the ubiquitin proteasome in pulmonary biology and disease.
abstract: Derangements in normal cellular homeostasis at the protein level can cause or be the consequence of initiation and progression of pulmonary diseases related to genotype, infection, injury, smoking, toxin exposure, or neoplasm. We discuss one of the fundamental mechanisms of protein homeostasis, the ubiquitin proteasome system (UPS), as it relates to lung disease. The UPS effects selective degradation of ubiquitinated target proteins via ubiquitin ligase activity. Important pathobiological mechanisms relating to the UPS and lung disease have been the focus of research, with inappropriate cellular proteolysis now a validated therapeutic target. We review the contributions of this system in various lung diseases, and discuss the exciting area of UPS-targeting drug development for pulmonary disease.
authors.affiliation: Acute Lung Injury Center of Excellence, Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pennsylvania, USA.
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Weathington
authors.forename: Jacob I
authors.initials: JI
authors.lastname: Sznajder
authors.forename: Rama K
authors.initials: RK
authors.lastname: Mallampalli
mesh_terms: D044783:F-Box Proteins / Q000502:physiology; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000502:physiology*; D008171:Lung Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology
chemical_list: D044783:F-Box Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex