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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
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1437-4315
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Volume 387, Issue 7

Issues

Impact of the N-terminal amino acid on targeted protein degradation

Thierry Meinnel
  • 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
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Alexandre Serero
  • 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 and Present address: Laboratoire de Radiobiologie de l'ADN, Service de Radiobiologie Molé culaire et Cellulaire CEA/CNRS UMR 217 Commissariat à l'Energie Atomique BP6, F-92 265 Fontenay aux Roses, France.
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Carmela Giglione
  • 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
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2006-07-20 | DOI: https://doi.org/10.1515/BC.2006.107

Abstract

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 ɛ-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.

Keywords: aminopeptidase; co-translational; deformylase; leucine; methionine; proteasome; protein; ubiquitin

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Published Online: 2006-07-20

Published in Print: 2006-07-01


Citation Information: Biological Chemistry, Volume 387, Issue 7, Pages 839–851, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2006.107.

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