The conserved protein ubiquitin acts as a signal for degradation in a multienzyme, energy-dependent proteolytic pathway.
Keywords: ubiquitin; ubiquitination; proteolysis; protein degradation; proteasome
Ubiquitin Pathway
Y Amy Lam, Johns Hopkins University, Baltimore, Maryland, USA
Cecile M Pickart, Johns Hopkins University, Baltimore, Maryland, USA
Published online: April 2001
DOI: 10.1038/npg.els.0000685
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Figure 1. Ubiquitin (Ub) pathway. DUB denotes a deubiquitinating enzyme. The symbol ‘~’ denotes a high-energy thioester bond.
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Figure 2. 26S proteasome. The representation of the 20S proteasome is based on crystal structures. The representation of the 19S complex is loosely based on electron tomographic images.
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Figure 3. The Sic1p-recognizing E3 from yeast (adapted from Hochstrasser,
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| References | |
| Bachmair A, Finley D and Varshavsky A (1986) In vivo half-life of a protein is a function of its amino-terminal residue. Science 234: 179–186. | |
| Chau V, Tobias JW, Bachmair A et al. (1989) A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243: 1576–1583. | |
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| Further Reading | |
| Baumeister W, Walz J, Zühl F and Seemüller E (1998) The proteasome: paradigm of a self-compartmentalizing protease. Cell 92: 367–380. | |
| Ciechanover A, Finley D and Varshavsky A (1984) Selective dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85. Cell 37: 57–66. | |
| Hershko A, Ciechanover A, Heller H, Haas AL and Rose IA (1980) Proposed role of ATP in protein breakdown: conjugation of proteins with multiple chains of the polypeptide of ATP-dependent proteolysis. Proceedings of the National Academy of Sciences of the USA 77: 1783–1786. | |
| Hicke L (1997) Ubiquitin-dependent internalization and down-regulation of plasma membrane proteins. FASEB Journal 11: 1215–1226. | |
| Lam YA, Xu W, DeMartino GN and Cohen RE (1997) Editing of ubiquitin conjugates by an isopeptidase in the 26S proteasome. Nature 385: 737–740. | |
| Pickart C M (1997) Targeting of substrates to the 26S proteasome. FASEB Journal 11: 1055–1066. | |
| book Rechsteiner M (ed.) (1988) Ubiquitin. New York: Plenum Press. | |
| Rock KL, Gramm C, Rothstein L et al. (1994) Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78: 761–771. | |
| Sommer T and Wolf D H (1997) Endoplasmic reticulum degradation: reverse protein flow of no return. FASEB Journal 11: 1227–1233. | |
| Varshavsky A (1996) The N-end rule: functions, mysteries, uses. Proceedings of the National Academy of Sciences of the USA 93: 12142–12149. | |
