title: Protein partners of deubiquitinating enzymes.
abstract: Protein modification by ubiquitin and ubiquitin-like molecules is a critical regulatory process. Like most regulated protein modifications, ubiquitination is reversible. Deubiquitination, the reversal of ubiquitination, is quickly being recognized as an important regulatory strategy. Nearly one hundred human DUBs (deubiquitinating enzymes) in five different gene families oppose the action of several hundred ubiquitin ligases, suggesting that both ubiquitination and its reversal are highly regulated and specific processes. It has long been recognized that ubiquitin ligases are modular enzyme systems that often depend on scaffolds and adaptors to deliver substrates to the catalytically active macromolecular complex. Although many DUBs bind ubiquitin with reasonable affinities (in the nM to microM range), a larger number have little affinity but exhibit robust catalytic capability. Thus it is apparent that these DUBs must acquire their substrates by binding the target protein in a conjugate or by associating with other macromolecular complexes. We would then expect that a study of protein partners of DUBs would reveal a variety of substrates, scaffolds, adaptors and ubiquitin receptors. In the present review we suggest that, like ligases, much of the regulation and specificity of deubiquitination arises from the association of DUBs with these protein partners.
authors.affiliation: Department of Biochemistry, Rollins Research Building, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Ventii
authors.forename: Keith D
authors.initials: KD
authors.lastname: Wilkinson
mesh_terms: D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D011506:Proteins; D025801:Ubiquitin; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex