Intracellular protein degradation

From a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting

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Abstract

Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code was transcribed to RNA and translated to proteins, but how proteins were degraded had 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 was largely non-lysosomal, but the mechanisms involved have 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 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. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.

Original languageEnglish
Pages (from-to)3-13
Number of pages11
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1824
Issue number1
DOIs
StatePublished - 1 Jan 2012

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Proteasome Endopeptidase Complex
Drug Delivery Systems
Ubiquitin
Lysosomes
Proteolysis
Degradation
Genetic Code
Proteins
Neurodegenerative Diseases
Quality Control
Organelles
Cell Cycle
Transcription Factors
Aberrations
RNA
Quality control
Cells
Research
Pharmaceutical Preparations
Neoplasms

Keywords

  • Diseases
  • Lysosome
  • Proteasome
  • Proteolysis
  • Ubiquitin

Cite this

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