The ubiquitin--proteasome system (UPS) consists of a series of enzymatic reactions wherein ubiquitin, a 76-amino-acid polypeptide, is conjugated onto specific lysine residues of a variety of protein substrates via conjugation. The fate of ubiquitinated proteins is determined by: the number of ubiquitin residues (ub-chains), the position of conjugations, and the specific branching patterns of poly-ubiquitin chains. Protein ubiquitination (Ub) is a reversible mechanism (deubiquitination) regulated by DUBs, which has emerged as a cardinal regulatory target for posttranslational modifications which, like protein phosphorylation, adds to the complexity and sensitivity of the UPS. DUBs are a class of the human family of proteases that remove ubiquitin or ubiquitin-like proteins from a variety of protein substrates. DUBs selectively cleave the isopeptide bond present at the C-terminus of ubiquitin molecule. DUBs regulate diverse cellular processes and functions including processing or removal of polyubiquitin moieties or chains on proteins, thereby altering the targeted protein’s fate with regard to either degradation by proteasome and/or differential subcellular localization. In addition, DUBs regulate gene expression, apoptosis, cell cycle, DNA repair as well as cytokine signaling.

References

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