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PMID: 19007437 Published · epublish English Journal Article Review

The ubiquitin system, disease, and drug discovery.

BMC biochemistry ·Vol. 9 Suppl 1 ·2008-10-21 ·Pages S7

Petroski MD

Abstract

The ubiquitin system of protein modification has emerged as a crucial mechanism involved in the regulation of a wide array of cellular processes. As our knowledge of the pathways in this system has grown, so have the ties between the protein ubiquitin and human disease. The power of the ubiquitin system for therapeutic benefit blossomed with the approval of the proteasome inhibitor Velcade in 2003 by the FDA. Current drug discovery activities in the ubiquitin system seek to (i) expand the development of new proteasome inhibitors with distinct mechanisms of action and improved bioavailability, and (ii) validate new targets. This review summarizes our current understanding of the role of the ubiquitin system in various human diseases ranging from cancer, viral infection and neurodegenerative disorders to muscle wasting, diabetes and inflammation. I provide an introduction to the ubiquitin system, highlight some emerging relationships between the ubiquitin system and disease, and discuss current and future efforts to harness aspects of this potentially powerful system for improving human health. PUBLICATION HISTORY : Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

MeSH Terms
Animals Cysteine Proteinase Inhibitors/therapeutic use Drug Discovery Humans Inflammation/drug therapy,metabolism Musculoskeletal Diseases/drug therapy,metabolism Mutation Neoplasms/drug therapy,metabolism Neurodegenerative Diseases/drug therapy,metabolism Proteasome Endopeptidase Complex/metabolism Proteasome Inhibitors Tumor Suppressor Protein p53/metabolism Ubiquitin/metabolism Ubiquitin-Protein Ligases/antagonists & inhibitors,metabolism Ubiquitination
Chemicals
Cysteine Proteinase Inhibitors Proteasome Inhibitors Tumor Suppressor Protein p53 Ubiquitin Ubiquitin-Protein Ligases Proteasome Endopeptidase Complex
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Petroski Matthew D
Rigel Pharmaceuticals, Inc, South San Francisco, CA, 94080, USA. petroski@burnham.org
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Article Info
Journal
BMC biochemistry
Abbr.
BMC Biochem
ISSN
1471-2091
DOI
10.1186/1471-2091-9-S1-S7
Email
petroski@burnham.org
Published
2008-10-21
Epub
2008-00-21
Pages
S7
Language
English
Region
England
NLM ID
101084098
PMCID
PMC2582801
Subset
IM
External Links
PubMed source DOI: 10.1186/1471-2091-9-S1-S7 PMC Full Text View journal details
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