Transcript Slide 52 - Sigma

Proteasome/Ubiquitination
SIGMA-ALDRICH
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).