Proteasome enzyme mechanism

On pharmacodynamic grounds, tumor resistance may be caused by such diverse mechanisms as the mutation or redundancy of topo II, the overexpression and preferred nuclear localization of proteasome a-type subunits (leading to a anomalous degradation of topo II), genetic deletion or loss-of-function mutations of p53, overexpression of ROS-detoxifying enzymes, overexpression of Bcl-2 (leading to a diminished cyt c release), etc. However, none of these factors would universally predict the development of anthracycline-resistance in a given tumor or another. 

Loss of muscle protein in trauma is caused by increased degradation rather than decreased synthesis. The degradation is controlled by changes in the levels of glucocorticoids, insulin and the proinflammatory cytokines TNFa and IL-1. The proteolytic enzyme complex that degrades the protein is the proteasome (Chapter 8). The mechanism by which the enzyme is activated is not known, but increased activities of the enzymes involved in ubiquitina-tion of proteins and an increase concentration of ubiquitin may play a role (Chapter 8). 

Suzuki T, Seko A, Kitajima K, Inoue Y, Inoue S (1994) Purification and enzymatic properties of peptide N-glycanase from C3H mouse-derived L-929 fibroblast cells Possible widespread occurrence of post-translational remodification of proteins by N-deglycosylation. J Biol Chem 269 17611-17618 Swaminathan S, Amerik AY, Hochstrasser M (1999) The Doa4 deubiquitinating enzyme is required for ubiquitin homeostasis in yeast. Mol Biol Cell 10 2583-2594 Tanaka K, Yoshimura T, Tamura T, Fujiwara T, Kumatori A, Ichihara A (1990) Possible mechanism of nuclear translocation of proteasomes. FEBS Lett 271 41-46... 

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