Ubiquitin and its role in proteolisis: the 2004 Nobel prize in chemistry

Abstract

In the early 1980-s, Aaron Ciechanover, Avram Hershko, and Irwin Rose discovered one of the most important cyclic cellular processes – a regulated ATP-dependent protein degradation, for which they were awarded the 2004 Nobel Prize in Chemistry. These scientists proved the existence of a non-lysosomal proteolysis pathway and completely changed the perception of intracellular protein degradation mechanisms. They demonstrated pre-labelling of a doomed protein in a cell with a biochemical marker called ubiquitin. Polyubiquitylation of a protein as a signal for its proteolysis was a new mechanism discovered as a result of collaborative efforts of three scientists on isolation of enzymes involved in this sequential process, clarification of the biochemical stages, and substantiating the energy dependence mechanism. The article contains biographical data of the Nobel laureates, the methods applied, and the history of the research resulted in the discovery of the phenomenon of proteasomal degradation of ubiquitin-mediated proteins. Keywords: PROTAC, regulated protein degradation, ubiquitin, І. Rose, А. Ciechanover, А. Hershko