Copyright© The Nobel Foundation 2004. We thank the Nobel Foundation, Stockholm, for permission to print this lecture.
Intracellular Protein Degradation: From a Vague Idea, through the Lysosome and the Ubiquitin–Proteasome System, and onto Human Diseases and Drug Targeting (Nobel Lecture)†
Article first published online: 5 SEP 2005
Copyright © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 44, Issue 37, pages 5944–5967, September 19, 2005
How to Cite
Ciechanover, A. (2005), Intracellular Protein Degradation: From a Vague Idea, through the Lysosome and the Ubiquitin–Proteasome System, and onto Human Diseases and Drug Targeting (Nobel Lecture). Angew. Chem. Int. Ed., 44: 5944–5967. doi: 10.1002/anie.200501428
- Issue published online: 14 SEP 2005
- Article first published online: 5 SEP 2005
- Manuscript Received: 26 APR 2005
- Nobel Lecture;
- protein breakdown;
Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis is largely non-lysosomal, but the mechanisms involved remained obscure. The discovery of the ubiquitin–proteasome system resolved the enigma. We now recognize that degradation of intracellular proteins is involved in regulation of a broad array of cellular processes, such as the cell cycle and division, regulation of transcription factors, and assurance of the cellular quality control. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of human disease, such as malignancies and neurodegenerative disorders, which led subsequently to an increasing effort to develop mechanism-based drugs.