Deubiquitinating Enzymes

Supporting information

Deubiquitinating enzymes (DUBs) are a group of proteases that catalyze the cleavage of protein-ubiquitin bonds. By removing these modifications, DUBs counteract the activity of ubiquitin ligases, which add ubiquitin molecules to target proteins.

USPs are the largest and best characterized of the DUB family. There are 63 putative human USP genes, and the proteins they encode are normally between 60 and 300 kDa in size. USPs cleave the isopeptide bond at the C-terminus of ubiquitin, preventing proteasomal degradation of specific proteins. By doing so, USPs also maintain a pool of ubiquitin within the cell and help to regulate protein localization and activation.

Deregulation of the ubiquitin-proteasome system (UPS) has been linked to numerous pathologies, including cancer and neurodegeneration; targeting mechanisms upstream of it may constitute an alternative to targeting the proteasome itself, as well as potentially sidestepping acquired resistance to proteasome inhibitors. Consequently, USP inhibitors are undergoing development as cancer therapeutics.

USP7 is particularly well-characterized; it stabilizes both p53 and MDM2, and has an integral role in cell death following DNA damage. Inhibition of USP14 has been shown to enhance resistance to oxidative stress, ostensibly by increasing proteasome activity and degradation of oxidized proteins.

In addition to USPs, other DUBs include UCH, OTU, MJD and JAMM classes. JAMM DUBs are zinc metalloprotease DUBs whereas the remaining groups are classified as cysteine proteases.

View all products for Deubiquitinating Enzymes »
Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Ubiquitin specific peptidase 7 Human USP7 NM_003479 Q93009
Mouse Usp7 NM_001003918 Q6A4J8
Rat Usp7 NM_001024790 Q4VSI4
Ubiquitin specific peptidase 14 Human USP14 NM_005151 P54578
Mouse Usp14 NM_021522 Q9JMA1
Rat Usp14 NM_001008301 -
View all Deubiquitinating Enzyme Gene Data »

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