Mechanism and function of deubiquitinating enzymes.

By A. Amerik, M. Hochstrasser. Biochimica et Biophysica Acta, 2004

1,022 citations recorded by the source corpus.

Attachment of ubiquitin to proteins is a crucial step in many cellular regulatory mechanisms and contributes to numerous biological processes, including embryonic development, the cell cycle, growth control, and prevention of neurodegeneration. In these diverse regulatory settings, the most widespread mechanism of ubiquitin action is probably in the context of protein degradation. Polyubiquitin attachment targets many intracellular proteins for degradation by the proteasome, and (mono)ubiquitination is often required for down-regulating plasma membrane proteins by targeting them to the vacuole (lysosome). Ubiquitin-protein conjugates are highly dynamic structures. While an array of enzymes directs the conjugation of ubiquitin to substrates, there are also dozens of deubiquitinating enzymes (DUBs) that can reverse the process. Several lines of evidence indicate that DUBs are important regulators of the ubiquitin system. These enzymes are responsible for processing inactive ubiquitin precursors, proofreading ubiquitin-protein conjugates, removing ubiquitin from cellular adducts, and keeping the 26S proteasome free of inhibitory ubiquitin chains. The present review focuses on recent discoveries that have led to a better understanding the mechanisms and physiological roles of this diverse and still poorly understood group of enzymes. We also discuss briefly some of the proteases that act on ubiquitin-like protein (UBL) conjugates and compare them to DUBs.

Subfields: Epidemiology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/3d6698705772bdd03a457f46f654fa7474e2681c

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Citations in the corpus

Riding the DUBway: regulation of protein trafficking by deubiquitylating enzymes (2006, neutral): “"”
The emerging shape of the ESCRT machinery (2007, background): “Many proteins that are involved in endocytic cargo sorting are ubiquitylated, and it has been proposed that another role of de-ubiquitylation might be to directly regulate the ESCRT machiner”
A genomic and functional inventory of deubiquitinating enzymes. (2005, neutral): “For detailed structural information see Amerik and Hochstrasser (2004).”
Origin and Function of Ubiquitin-like Protein Conjugation (2009, background): “In eukaryotes, specific JAMM-class proteases act as deubiquitylating enzymes (DUBs) or UBL-specific proteases (ULPs”
Regulation and Cellular Roles of Ubiquitin-specific Deubiquitinating Enzymes (2009, background): “-) also known as the Josephin domain with specificity for ubiquitin-like proteins (17, 18).”
One step at a time: endoplasmic reticulum-associated degradation (2008, background): “Members of this growing family of enzymes can catalyse the en bloc removal of polyubiquitin moieties or catalyse the trimming of the polyubiquitin chai”