Ubiquitin-proteosome system

Fig. 2.17. Degradation of the tumor suppressor protein p53 by the ubiquitin-proteosome system. The oncoprotein E6 of the human papilloma virus (HPV) forms a specific complex with the p53 protein and can thus induce the degradation of p53. The E6-p53 complex is recognized by E6-AP, a E3 enzyme of the ubiquitin pathway, as a target protein, whereby a ubiquitin residue is transferred to a lysine residue of p53. In this process, the E6 protein serves as the recognition element for ubiquitin hgation of p53.

More recently we have investigated whether the ubiquitin-proteosome system is perturbed in the heart of human DCM patients (Weekes et al, 2003). As in bovine DCM, expression of the enzyme UCH was elevated more than 8-fold at the protein level and elevated more than 5-fold at the mRNA level in human DCM. Moreover, this increased expression of UCH was shown by immuno-cytochemistry to be associated with the myocytes, which do not exhibit detectable staining in control hearts. Overall protein ubiquitination was increased 5-fold in DCM relative to control hearts. Using a selective affinity purification method we were able to demonstrate enhanced ubiquitination of a number of distinct proteins in DCM hearts. We have identified a number of these proteins by mass spectrometry. Interestingly many of these proteins were the same proteins previously found to be present at reduced abundance in DCM hearts (Corbett et al, 1998). This new evidence strengthens our hypothesis that inappropriate ubiquitin conjugation leads to proteolysis and depletion of certain proteins in the DCM heart and may contribute to loss of normal cellular function in the diseased heart. 

The Role of the Ubiquitin-Proteosome System and Autophagy Pathways... 

Muscle PB is the result of proteolysis. There are two main processes through which proteins in general may be degraded the autophagic-lysomal pathway and the ubiquitin-proteosome pathway.4 Both of these systems are present in skeletal muscle, yet their contribution to total PB is not yet fully understood. However, the... 

While chaperonins assist proteins to fold correctly proteasomes destroy unfolded chains by partial hydrolysis, cutting the chains into a random assortment of pieces from 3 to 30 residues in length with an average length of 8 residues/ Proteasomes destroy not only unfolded and improperly folded proteins but also proteins marked for destruction by the ubiquitin system described in Box 10-C. It has been hard to locate true proteosomes in most bacteria. However, they do contain protease particles with similar characteristics2-1 and archaeons, such as Thermoplasma acidophilum, have proteasomes similar to those of eukaryotes.cc... 

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