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Proteolysis: from the lysosome to ubiquitin and the proteasome

Nature Reviews Molecular Cell Biology volume 6, pages 79–87 (2005)Cite this article

Abstract

How the genetic code is translated into proteins was a key focus of biological research before the 1980s, but how these proteins are degraded remained a neglected area. With the discovery of the lysosome, it was suggested that cellular proteins are degraded in this organelle. However, several independent lines of experimental evidence strongly indicated that non-lysosomal pathways have an important role in intracellular proteolysis, although their identity and mechanisms of action remained obscure. The discovery of the ubiquitin–proteasome system resolved this enigma.

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Figure 1: The lysosome.
Figure 2: Some of the various functions of modification by ubiquitin and ubiquitin-like proteins.

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Acknowledgements

A.C. is supported by: the Prostate Cancer Foundation (PCF) Israel — Centers of Excellence Program; the Israel Science Foundation — Centers of Excellence Program; a Professorship that is funded by the Israel Cancer Research Fund (ICRF) USA; and the Foundation for Promotion of Research in the Technion. Infrastructural equipment for experimental work in the Cancer and Vascular Biology Center, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel, has been purchased with the support of the Wolfson Charitable Fund — Center of Excellence for studies on the turnover of cellular proteins and its implications to human diseases.

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  1. the Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Efron Street, Bat Galim, PO Box 9649, Haifa, 31096, Israel

    Aaron Ciechanover

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DATABASES

Entrez

Lon

Saccharomyces genome database

Apg12

Swiss-Prot

ubiquitin

SUMO

FURTHER INFORMATION

Pfam: Ubiquitin family

Prolysis

Protein Degradation

Regulated Protein Turnover Resources Site: Ubiquitin Ligases and Diseases

The Pathway of Protein Ubiquitinylation

The Proteasome

The Proteasomes

The Ubiquitin System

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Ciechanover, A. Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6, 79–87 (2005). https://doi.org/10.1038/nrm1552

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