Ubiquitin protein degradation

In addition to protein proteolysis during mitosis, ubiquitin-mediated protein degradation ( ubiquitin/ proteasome) is also required at the G1 to S transition... 

In ubiquination, the major mechanism of protein degradation, ubiquitin (a small hsp) is covalently attached to lysine residues of a protein with structural features such as oxidized amino acid residues that mark it for destruction. Once the protein is ubiquinated it is degraded by proteases in ATP-requiring reactions. 

Varshavsky and colleagues have also characterized a nonlysosomal protein-degradation pathway in eukaryotic cells, primarily in yeast. In addition to confirming that the N-end rule applies to eukaryotic proteins as well, they identified a 76-amino-acid protein called ubiquitin as one of the major signals for protein degradation. Ubiquitin got its name because it is found in essentially every cell type ever examined. The sequence of ubiquitin is almost identical in yeast and humans,... 

Ubiquitin tags proteins for protein degradation. The ubiquitination requires three different enzymatic activities, a ubiquitin-activating enzyme (El), a ubiquitin-conjugating enzyme (E2 or Ubc) and a ubiquitin ligase (E3). The action of all three enzymes leads to the establishment of a poly-ubiquitin chain on target proteins which are then recognized and proteolyzed by the 26S proteasome. 

Hershko, A. (1988). Ubiquitin-mediated protein degradation. J. Biol. Chem. 263, 15237-15240. 

The proteasome is a cytoplasmic protein degradation machine that hydrolyses proteins, which have been designated for degradation by having a number of molecules of the small ubiquitous protein, ubiquitin, attached to them. 

Brief History of Protein Degradation and the Ubiquitin System... 

In the initial experiments, we resolved reticulocyte lysates on DEAE-cellulose into two crude fractions Fraction 1, which contained proteins not adsorbed to the resin, and Fraction 2, which contained all proteins adsorbed to the resin and eluted with high salt. The original aim of this fractionation was to get rid of hemoglobin, which was known to be in Fraction 1, while most non-hemoglobin proteins of reticulocytes were known to be in Fraction 2. We found that neither fraction was active by itself, but ATP-dependent protein degradation could be reconstituted by combination of the two fractions [13]. The active component in Fraction 1 was a small, heat-stable protein we have exploited its stability to heat treatment for its purification to near homogeneity. We termed this protein at that time APF-1, for ATP-dependent Proteolysis Factor 1 [13]. The identity of APF-1 with ubiquitin was established later by Wilkinson et al. [14], subsequent to the discovery in my laboratory of its covalent ligation to protein substrates, as described below. 

Evolutionary Origin of the Activation Step During Ubiquitin-dependent Protein Degradation... 

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