Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology.
Cellular proteins are in a dynamic state maintained by synthesis and degradation. The ubiquitin proteolytic pathway is responsible for the degradation of the bulk of cellular proteins including short-lived, regulatory, and misfolded/denatured proteins. Ubiquitin-mediated proteolysis involves covalent attachment of multiple ubiquitin molecules to the protein substrate and degradation of the targeted protein by the 26S proteasome. Recent understanding of the molecular mechanisms involved provides a framework to understand a wide variety of human pathophysiological states as well as therapeutic interventions. This review focuses on the response to hypoxia, inflammatory diseases, neurodegenerative diseases, and muscle-wasting disorders, as well as human papillomaviruses, cervical cancer and other malignancies.
Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri 63110, USA. schwartz@wustl.edu
Alan L
AL
Schwartz
Aaron
A
Ciechanover
D000818:Animals; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000503:physiopathology; D009220:Myositis / Q000378:metabolism / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism / Q000821:virology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021381:Protein Transport; D014452:Ubiquitins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000378:metabolism / Q000821:virology
D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease