Regulating the regulators: control of protein ubiquitination and ubiquitin-like modifications by extracellular stimuli.

Like many other posttranscriptional modifications, ubiquitination and conjugation of ubiquitin-like polypeptides to target proteins are tightly regulated by extracellular stimuli. In many cases, this regulation is dependent upon protein phosphorylation. The regulatory step affected by phosphorylation could involve either recognition of the substrate by an E3 ubiquitin ligase or the actual conjugation reaction. Regulation occurs through phosphorylation of either the substrates or the E3 ligases themselves. This review focuses on recent advances in understanding how extracellular stimuli modulate the attachment of ubiquitin and ubiquitin-like peptides to target proteins.