Impact of the N-terminal amino acid on targeted protein degradation.
The N-terminus of any protein may be used as a destabilization signal for targeted protein degradation. In the eukaryotic cytosol, the signal - the so-called N-degron--is recognized for degradation by (i) the N-end rule, a well-described degradation process involving epsilon-ubiquitination; or (ii) N-terminal ubiquitination, a more recently described pathway. Dedicated E3 ubiquitin ligases known as N-recognins then act on the protein. The proteolytic pathways involve ATP-dependent chambered proteases, such as the 26S proteasome in the cytosol, which generate short oligopeptides. The N-terminus of the polypeptide chain is also important for post-proteasome degradation by specific aminopeptidases, which complete peptide cleavage to generate free amino acids. Finally, in each compartment of the eukaryotic cell, N-terminal methionine excision creates a variety of N-termini for mature proteins. It has recently been shown that the N-terminal methionine excision pathway has a major impact early in targeted protein degradation.
Meinnel
Thierry
T
Protein Maturation, Cell Fate and Therapeutics, Institut des Sciences du Végétal, UPR2355, Centre National de la Recherche Scientifique, Bâtiment 23, 1 avenue de la Terrasse, F-91198 Gif-sur-Yvette cedex, France. meinnel@isv.cnrs-gif.fr
Serero
Alexandre
A
Giglione
Carmela
C
D000215:Acylation; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D006868:Hydrolysis; D008969:Molecular Sequence Data; D015388:Organelles / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D000596:Amino Acids; D011506:Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases