Proteasome/Ubiquitination

1. Proteasome/Ubiquitination SIGMA-ALDRICH

2. Proteasome/Ubiquitination Attachment of ubiquitin to proteins targets them for proteolytic degradation by a complex cellular structure, the proteasome. Degradation of proteins by proteasomes removes denatured, damaged or improperly translated proteins from cells and regulates the level of proteins such as cyclins and some transcription factors. E1 and E2 enzymes prepare the ubiquitin chains that are then attached to proteins by the E3 enzyme. The core proteasome (20S proteasome) consists of four rings each with 14 subunits stacked on top of each other that are responsible for the proteolytic activity of the proteasome. The PA700 regulatory complex is stacked on the ends of the cylindrical core to form a 26S proteasome. Proteins that are tagged with ubiquitin are recognized and bound by the regulatory subunits, then unfolded in an ATP-dependent manner, and inserted into the core particle, where proteases degrade the protein, releasing small peptides and releasing the ubiquitin intact. The PA28 regulatory complex is an alternative regulatory complex that appears to play a role in antigen processing for presentation of peptides to immune cells in the major histocompatibility complex I (MHC I) complex. 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).