Targeting Proteins for Destruction by the Ubiquitin System: Implications for Human Pathobiology
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- 1 February 2009
- journal article
- review article
- Published by Annual Reviews in Annual Review of Pharmacology and Toxicology
- Vol. 49 (1) , 73-96
- https://doi.org/10.1146/annurev.pharmtox.051208.165340
Abstract
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.Keywords
This publication has 148 references indexed in Scilit:
- Oxygen Sensing by Metazoans: The Central Role of the HIF Hydroxylase PathwayMolecular Cell, 2008
- Autophagosome formation: core machinery and adaptationsNature Cell Biology, 2007
- Mutant ubiquitin found in Alzheimer's disease causes neuritic beading of mitochondria in association with neuronal degenerationCell Death & Differentiation, 2007
- RACK1 Competes with HSP90 for Binding to HIF-1α and Is Required for O2-Independent and HSP90 Inhibitor-Induced Degradation of HIF-1αMolecular Cell, 2007
- Drug discovery in the ubiquitin–proteasome systemNature Reviews Drug Discovery, 2006
- Activation of IKK by TNFα Requires Site-Specific Ubiquitination of RIP1 and Polyubiquitin Binding by NEMOMolecular Cell, 2006
- Autophagy: molecular machinery for self-eatingCell Death & Differentiation, 2005
- NF-κB: linking inflammation and immunity to cancer development and progressionNature Reviews Immunology, 2005
- Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin–proteasome system and onto human diseases and drug targetingCell Death & Differentiation, 2005
- Biological activities and molecular targets of the human papillomavirus E7 oncoproteinOncogene, 2001