Ubiquitin-Proteasome Pathway

1. Ubiquitin-Proteasome Pathway SIGMA-ALDRICH

2. Ubiquitin-Proteasome Pathway Intracellular proteolytic systems recognize and destroy misfolded or damaged proteins, unassembled polypeptide chains, and short-lived regulatory proteins. There are several mechanisms for protein degradation within cells. Two systems that play important roles in proteolysis resulting from cell stress are the calpain proteases and the ubiquitin-proteasome pathway. The ubiquitin-proteasome pathway functions widely in intracellular protein turnover. It plays a central role in degradation of short-lived and regulatory proteins important in a variety of basic cellular processes, including regulation of the cell cycle, modulation of cell surface receptors and ion channels, and antigen processing and presentation. The pathway employs an enzymatic cascade by which multiple ubiquitin molecules are covalently attached to the protein substrate. The polyubiquitin modification marks the protein for destruction and directs it to the 26S proteasome complex for degradation. References Sommer, T., et al., Compartment - specific functions of the ubiquitin - proteasome pathway. Rev. Physiol. Biochem. Pharmacol., 142, 97-160 (2001). Doskeland, A.P., and Flatmark, T., Conjugation of phenylalanine hydroxylase with polyubiquitin chains catalysed by rat liver enzymes. Biochim. Biophys. Acta., 1547, 379-386 (2001). Hartmann-Petersen, R., et al., Quaternary structure of the ATPase complex of human 26S proteasomes determined by chemical cross-linking. Arch. Biochem. Biophys., 386, 89-94 (2001). Brooks, P., et al., Subcellular localization of proteasomes and their regulatory complexes in mammalian cells. Biochem. J., 346, 155-161 (2000).