Overview
Since the modest beginnings of its discovery in the late 1970’s, ubiquitination
has emerged as a central and critical process involved in the regulation of
virtually all cellular activities. Ubiquitin (Ub) is a small (76 kDa)
highly conserved protein ubiquitously expressed in eukaryotic
organisms. The conjugation of ubiquitin to proteins is an important
means to regulate protein function by targeting tagged proteins for
proteasomal degradation and modifying their activity. The
modification of target proteins by ubiquitination is reversible, and the
removal of Ub can rescue proteins from degradation or re-modulate their
activity. The deconjugation of ubiquitin is accomplished by the
deubiquitinating enzymes (DUBs). The majority of DUBs in the human
genome belong to the ubiq uitin specific protease (USP) subclass of DUBs.
Structurally, USPs contain a common catalytic domain that consists of two
short well-conserved motifs, called Cys and His boxes.
Similar to the action of ubiquitination being involved in most cellular
activities, deubiquitination by USPs has also been established as a
critical aspect of many cellular processes and is viewed as a critical
regulatory mechanism in the cell. USPs have been noted to be involved
in apoptosis, the
cell cycle, cell
division, DNA
damage repair, chromatin and histone
modification, cytoskeletal
organization, neurodevelopment, RNA
processing, transcription, translation, transport, signal
transduction and the
regulation of kinase activity. Research on the regulation of
these enzymes is only in its beginning phase, and more information on this aspect
of USP biology will help to further delineate the cycle of ubiquitination.
