Ubiquitin-dependent protein degradation: a cellular perspective

Abstract

A major pathway for protein degradation in eukaryotes is ubiquitin dependent. Substrate-specific ubiquitin-conjugating enzymes and accessory factors recognize specific signals on proteolytic substrates and attach ubiquitin to defined lysine residues of substrate proteins. Ubiquitin-protein conjugates are then degraded by the proteasome, a multicatalytic protease complex. This proteolytic pathway is highly selective and tightly regulated. It mediates the elimination of abnormal proteins and controls the half-lifes of certain regulatory proteins. Targets include transcriptional regulators, p53 and cyclins, pointing to a role of the ubiquitin system in the regulation of gene expression and growth control.