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Author Notes:

Corresponding author. Requests for reprint: Keith D. Wilkinson, Emory University, Department of Biochemistry, 1510 Clifton Road, Room 4017, Rollins Research Building, Atlanta, GA 30322 USA. Phone: 404-727-5980; Fax: 404-727-3452; Email: genekdw@emory.edu.

Francisca E. Reyes-Turcu was a member of the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia when this article was written.

Keith D. Wilkinson has intellectual property arrangements with Boston Biochem and Biomol International, LP, both of whom sell some of the reagents mentioned in this review.

Francisca E. Reyes-Turcu and Karen H. Ventii are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review.

Subjects:

Keywords:

  • Ubiquitin
  • Proteasome
  • Histone
  • Cell cycle
  • Endocytosis
  • DNA Damage
  • Signal Transduction

Regulation and Cellular Roles of Ubiquitin-specific Deubiquitinating Enzymes

Tools:

Journal Title:

Annual Review of Biochemistry

Volume:

Volume 78

Publisher:

, Pages 363-397

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Deubiquitinating enzymes (DUBs) are proteases that process ubiquitin or ubiquitin-like gene products, reverse the modification of proteins by a single ubiquitin (or ubiquitin-like protein), and remodel polyubiquitin (or ubiquitin-like) chains on target proteins. The human genome encodes nearly 100 DUBs with specificity for ubiquitin in five families: the UCH, USP, OTU, Josephin, and JAMM families. Four families are cysteine proteases, while the later is a family of metalloproteases. Most DUB activity is cryptic and active site rearrangements often occur during the binding of ubiquitin and/or scaffold proteins. DUBs with specificity for ubiquitin contain multiple domains with insertions and extensions modulating DUB substrate specificity, protein-protein interactions, and cellular localization. Binding partners and multi-protein complexes with which DUBs associate modulate DUB activity and substrate specificity. Quantitative studies of activity and protein-protein interactions, together with genetic studies and the advent of RNAi, have lead to new insights into the function of yeast and human DUBs. This review will discuss ubiquitin-specific DUBs, some of the generalizations emerging from recent studies of the regulation of DUB activity, and their roles in various cellular processes. Specific examples are drawn from studies of protein degradation, DNA repair, chromatin remodeling, cell cycle regulation, endocytosis, and modulation of signaling kinases.

Copyright information:

© 2009 by Annual Reviews

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