Proteosomes

Proteosomal degration is the process by which improperly folded proteins or proteins with altered post-translational modifications are removed from a cell before they have a detrimental effect on cellular function. This is performed in small organelles known as proteosomes. Proteins are targeted for destruction in the proteosome by having a number of small ubiquitin molecules added. 

Proteosomal Degradation Prothrombin Time Protocadherins Protocidal Drugs... 

Hsp90 is a molecular chaperon required for the refolding of proteins in cells exposed to environmental stress. It contains an ATP-binding pocket in its amino terminus. Several natural products, for example radicicol (230) (Scheme 48), bind to this pocket and inhibit its chaperon function, which is mirrored in enhanced proteosomal degradation of Hsp90 client proteins, so that compounds like 230 are of interest as novel anticancer agents. 

Proteosome An enzyme complex that degrades intracellular proteins. 

Proteins which are destined for degradation by the proteosome are first modified by the enzyme-catalysed attachment of numerous molecules of the protein ubiquitin, through amino groups to the protein targeted for degradation. This marks out the protein for ATP-dependent hydrolysis by the 26S proteosome, releasing peptides and ubiquitin... 

Iwai etal, 1995 Guo etal, 1995). It seems therefore highly probable that the proteosome (and also ubiquitinylation) is involved in IRP-2 degradation. 

Orr N, Robin G, Cohen D, Arnon R, Lowell GH Immunogenicity and efficacy of oral or intranasal Shigella flexneri 2a and Shigella sonnei proteosome-lipopolysaccharide vaccines in animal models. Infect Immun 1993 61 2390-2395. 

VON DEE Lehr, N. et al. The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. Mol Cell 2003, 33, 1189-200. 

Levi R, et al. Intranasal immunization of mice against influenza with synthetic peptides anchored to proteosomes. Vaccine 1995 13 1353. 

FIG. 5. Role of phosphorylation and degradation of clock protein PER in human normal fibroblasts. After the phosphorylation of hPERl by casein kinase, the ubiquitin-proteosome pathway may be involved in its degradation in human cells. 

---