Experimental and Molecular Medicine (Jul 2018)
Control of protein degradation by N-terminal acetylation and the N-end rule pathway
Abstract
Protein Nα-terminal acetylation: Regulating stability The addition of an acetyl group to amino acids at the start of a protein (known as the Nα-terminal end) is crucial for maintaining protein homeostasis and cellular health. Hwang and colleagues review the effects of Nα-terminal acetylation (Nt-acetylation) on protein function and stability. This modification occurs in over 50% of proteins in eukaryotic organisms and when mis-regulated can lead to cancer, hypertension, neurodegeneration etc. Nt-acetylation not only targets proteins for degradation through a specific signaling pathway, but also regulates protein folding, cellular localization and activity. This seemingly irreversible modification can also protect proteins against other mechanisms of degradation and represents a potential therapeutic target. Inhibiting Nt-acetylation-dependent protein interactions could be a useful strategy for regulating protein stability.