Targeting of substrates to the 26S proteasome.
The ubiquitin-proteasome pathway is the principal mechanism for the turnover of short-lived proteins in eukaryotic cells. In this pathway, the covalent ligation of ubiquitin to the substrate is a signal for recognition by the 26S proteasome. Recent studies indicate that targeting of substrates of the ubiquitin pathway to the proteasome is usually accomplished by the ligation of a polyubiquitin chain assembled through K48-G76 isopeptide bonds, rather than by ligation of monoubiquitin. In addition to providing benefits in signal generation, recognition, and persistence, assigning the proteolytic targeting function to a specific specific type of polyubiquitin chain may allow monoubiquitin or polyubiquitin chains of novel structures to serve distinct targeting functions. Besides polyubiquitinated substrates, the proteasome also degrades an unknown number of proteins that are recognized without undergoing ubiquitination. Ornithine decarboxylase is the prototype ubiquitin-independent substrate; it is targeted to the proteasome through noncovalent interaction with a specific protein factor known as antizyme. The existence of ubiquitin-independent substrates of the proteasome raises important questions about the nature of the substrate- and proteasome-based elements that cooperate to bring about the targeting of substrates to this novel proteolytic complex.
Pickart
C M
CM
Department of Biochemistry, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
D000818:Animals; D001665:Binding Sites; D046911:Macromolecular Substances; D008961:Models, Structural; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D017433:Protein Structure, Secondary; D015398:Signal Transduction; D013379:Substrate Specificity; D014452:Ubiquitins / Q000378:metabolism*
D046911:Macromolecular Substances; D014452:Ubiquitins; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D009955:Ornithine Decarboxylase