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

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Published/Copyright: July 20, 2006
Biological Chemistry
From the journal Volume 387 Issue 7

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.

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References

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Published Online: 2006-07-20
Published in Print: 2006-07-01

©2006 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. 4th General Meeting of the International Proteolysis Society/International Conference on Protease Inhibitors
  2. Extracellular granzymes: current perspectives
  3. Impact of the N-terminal amino acid on targeted protein degradation
  4. Structural aspects of recently discovered viral deubiquitinating activities
  5. Cysteine cathepsins and caspases in silicosis
  6. The proprotein convertases and their implication in sterol and/or lipid metabolism
  7. PREPL: a putative novel oligopeptidase propelled into the limelight
  8. Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double-deficient mice
  9. Helicobacter pylori-induced downregulation of the secretory leukocyte protease inhibitor (SLPI) in gastric epithelial cell lines and its functional relevance for H. pylori-mediated diseases
  10. Increased local levels of granulocyte colony-stimulating factor are associated with the beneficial effect of pre-elafin (SKALP/trappin-2/WAP3) in experimental emphysema
  11. Interaction of a novel form of Pseudomonas aeruginosa alkaline protease (aeruginolysin) with interleukin-6 and interleukin-8
  12. Analysis of aldosterone-induced differential receptor-independent protein patterns using 2D-electrophoresis and mass spectrometry
  13. Modeling the 3D structure of wheat subtilisin/chymotrypsin inhibitor (WSCI). Probing the reactive site with two susceptible proteinases by time-course analysis and molecular dynamics simulations
  14. A stable analogue of glucose-dependent insulinotropic polypeptide, GIP(LysPAL16), enhances functional differentiation of mouse embryonic stem cells into cells expressing islet-specific genes and hormones
  15. Transcription factor FOXM1c is repressed by RB and activated by cyclin D1/Cdk4
  16. Despite its strong transactivation domain, transcription factor FOXM1c is kept almost inactive by two different inhibitory domains
  17. Inhibition of calcineurin by infusion of CsA causes hyperphosphorylation of tau and is accompanied by abnormal behavior in mice
  18. Isolation and properties of extracellular proteinases of Penicillium marneffei
  19. Isolation and comparative characterization of Ki-67 equivalent antibodies from the HuCAL® phage display library
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