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Nat Rev Mol Cell Biol. 2005 Jan;6(1):79-87. doi: 10.1038/nrm1552.

Proteolysis: from the lysosome to ubiquitin and the proteasome.

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


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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