Chemistry-Based Functional Proteomics: Mechanism-Based Activity-Profiling Tools for Ubiquitin and Ubiquitin-like Specific Proteases

Joris Hemelaar, Paul J. Galardy, Anna Borodovsky, Benedikt M. Kessler, Hidde L. Ploegh, Huib Ovaa

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Determining the biological function of newly discovered gene products requires the development of novel functional approaches. To facilitate this task, recent developments in proteomics include small molecular probes that target proteolytic enzyme families including serine, threonine, and cysteine proteases. For the families of ubiquitin (Ub) and ubiquitin-like (UBL)-specific proteases, such tools were lacking until recently. Here, we review the advances made in the development of protein-based active site-directed probes that target proteases specific for ubiquitin and ubiquitin-like proteins. Such probes were applied successfully to discover and characterize novel Ub/UBL-specific proteases. Ub/UBL processing and deconjugation are performed by a diverse set of proteases belonging to several different enzyme families, including members of the ovarian tumor domain (OTU) protease family. A further definition of this family of enzymes will benefit from a directed chemical proteomics approach. Some of the Ub/UBL-specific proteases react with multiple Ub/UBLs and members of the same protease family can recognize multiple Ub/UBLs, underscoring the need for tools that appropriately address enzyme specificity.

Original languageEnglish (US)
Pages (from-to)268-276
Number of pages9
JournalJournal of Proteome Research
Volume3
Issue number2
DOIs
StatePublished - Mar 2004
Externally publishedYes

Fingerprint

Ubiquitin-Specific Proteases
Ubiquitin
Proteomics
Peptide Hydrolases
Enzymes
Ubiquitins
Molecular Probes
Cysteine Proteases
Serine Proteases
Threonine
Catalytic Domain
Serine
Tumors
Genes

Keywords

  • Activity-based inhibitor
  • Functional proteomics
  • Intein
  • Nedd8
  • Protease profiling
  • Suicide inhibitor
  • SUMO
  • Ubiquitin
  • Ubiquitin-like protein
  • Ubiquitin-specific protease

ASJC Scopus subject areas

  • Genetics
  • Biotechnology
  • Biochemistry

Cite this

Chemistry-Based Functional Proteomics : Mechanism-Based Activity-Profiling Tools for Ubiquitin and Ubiquitin-like Specific Proteases. / Hemelaar, Joris; Galardy, Paul J.; Borodovsky, Anna; Kessler, Benedikt M.; Ploegh, Hidde L.; Ovaa, Huib.

In: Journal of Proteome Research, Vol. 3, No. 2, 03.2004, p. 268-276.

Research output: Contribution to journalArticle

Hemelaar, Joris ; Galardy, Paul J. ; Borodovsky, Anna ; Kessler, Benedikt M. ; Ploegh, Hidde L. ; Ovaa, Huib. / Chemistry-Based Functional Proteomics : Mechanism-Based Activity-Profiling Tools for Ubiquitin and Ubiquitin-like Specific Proteases. In: Journal of Proteome Research. 2004 ; Vol. 3, No. 2. pp. 268-276.
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