Proteolysis: from the lysosome to ubiquitin and the proteasome


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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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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Saccharomyces genome database






Pfam: Ubiquitin family


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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).

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