The ubiquitin proteasome system with its checks and balances

Abstract

Cells need to quickly change according to changing environment to survive, and for that, they must not just make new proteins but also degrade others equally promptly. For this purpose, cells have evolved the ubiquitin system, which consists of ubiquitin molecules which are used to tag proteins in a process called ubiquitination; E1, E2 and E3 enzymes which carry out the process of ubiquiti- nation; and deubiquitinating enzymes (DUBs) that remove the ubiquitin from the substrate proteins in a process called deubiquitination. Ubiquitination involves various lysine residues on ubiquitin; among them K48 and K63 are the most significant and well understood. Ubiquitination with K48 linkage leads to degradation of substrate proteins by a multi-protein complex called proteasome. Proteasome-mediated degradation is involved in numerous different processes in cells, due to which defects in it are responsible for several diseases. But due to the high diversity of E3 enzymes and ubiquitin target proteins, there are many drug targets that can be utilized to treat diseases. This makes it vital to understand ubiquitin system for advancement of health care.