Protein degradation and regulation - shutcm - 首 页.pptVIP

Protein Degradation and Regulation Ubiquitin/Proteasome Pathway Guo Peng, Luo Tong and Yang Kong2002.12.16 I. Introduction This pathway is the major non-lysosomal process responsible for the breakdown of most short and long-lived proteins in mammalian cells. For example, in skeletal muscle, the system is responsible for the breakdown of the major contractile proteins, actin and myosins. In addition, the pathway also controls various major biological events: cellcycle progression, oncogenesis, transcriptional control, development and differentiation, signal transduction, receptor down-regulation and antigen processing, via the breakdown of specific proteins. Cellular functions of protein degradation The elimination of damaged proteins: environmental toxins, translation errors and genetic mutations can damage proteins. Misfolded proteins are highly deleterious to the cell because they can form non-physiological interactions with other proteins. Repair proteins called chaperones can, in many instances, restore the native conformation of misfolded proteins. However, if a damaged protein is not repaired, it is degraded in specialized organelles such as the ysosome, and by the ubiquitin/proteasome pathway. Mislocalized proteins and stoichiometric excess Some proteins are stabilized only when they are bound to their natural partners. This ensures that they are present only at stoichiometric levels. Consequently, the overexpression of specific ribosomal proteins can lead to degradation because of their failure to assemble into the ribosome. Similarly, proteinsthat are mislocalized may be degraded because they are unable to form interactions that normally stabilize them. Retro-translocation Proteins that enter the secretory pathway and fold improperly in the endoplasmic reticulum are transported back to the cytosol where they are recognized and degraded by the ubiquitin/proteasome pathway. Degradation of foreign proteins The immune system