Proteasomes Protein

What are the relationships of Lewy body formation, proteasomal protein degradation and mitochondrial dysfunction to parkinsonism (see ref. [8] for a detailed review). 

Rape, M. and Jentsch, S. Taking a bite proteasomal protein processing. 

Peters, J-M. (1994) Proteasomes protein degradation machines of the cell. Trends Biochem. Sci. 19, 377-382. 

Considering the highly processive mechanism of the protein degradation by the proteasome, a question naturally arises what is a mechanism behind such translocation rates Let us discuss one of the possible translocation mechanisms. In [52] we assume that the proteasome has a fluctuationally driven transport mechanism and we show that such a mechanism generally results in a nonmonotonous translocation rate. Since the proteasome has a symmetric structure, three ingredients are required for fluctuationally driven translocation the anisotropy of the proteasome-protein interaction potential, thermal noise in the interaction centers, and the energy input. Under the assumption that the protein potential is asymmetric and periodic, and that the energy input is modeled with a periodic force or colored noise, one can even obtain nonmonotonous translocation rates analytically [52]. Here we... 

The damaged, misfolded proteins aggregate, and overwhelm the ubiquitin/proteasome protein degradation... 

Keywords Proteasome Protein oxidation Protein degradation Protein repair... 

Proteasomes are the major cytosolic and nuclear protein degradation machineries and they are also responsible for the proteolysis of misfolded, ER-dislocated (endoplasmic reticulum) proteins [1-3]. Proteasomal protein turnover takes place in an ubiquitin-dependent manner. The proteasome-generated products - ohgopeptides varying in length from 3 to up to 30 amino acid residues - are further processed by aminopeptidases. In higher vertebrates, antigenic peptides are selected from the peptide pool produced by proteasomes and downstream aminopeptidases for presentation on the outer cell surface by major histocompatibility class 1 (MHCl) protein complexes. In this way, proteasomes are essential factors in the detection and eradication of virally infected cells. 

Ubiquitin-proteasome pathway, involved in the degradation of tumor growth proteins, plays an important role in the treatment of cancer. Physalin B (6), the major steroidal lactone of Physalis angulata, is known to produce the ubiquitinated protein accumulation and inhibit the TNFa-induced activation of NF-KB in DLD-1 4Ub-Luc cell assay. Physalin B does not inhibit purified proteasome catalytic activities but interferes with the cellular catalytic activities of the proteasome proteins at 4—8-fold high concentration, which is required to produce significant rise in bioluminescence and ubiquitinated protein accumulation in DLD-1 4Ub-Luc cells. The results indicate that physalin B is cytotoxic and works as an apoptotic triggering agent in DLD-1 4Ub-Luc cells [95]. 

---