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Science 10 October 1986: Vol. 234. no. 4773, pp. 179 - 186 DOI: 10.1126/science.3018930
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Articles
Science, Vol 234, Issue 4773, 179-186
Copyright © 1986 by American Association for the Advancement of Science
In vivo half-life of a protein is a function of its amino-terminal residue
A Bachmair,
D Finley,
and
A Varshavsky
When a chimeric gene encoding a ubiquitin-beta-galactosidase fusion protein is expressed in the yeast Saccharomyces cerevisiae, ubiquitin is cleaved off the nascent fusion protein, yielding a deubiquitinated beta-galactosidase (beta gal). With one exception, this cleavage takes place regardless of the nature of the amino acid residue of beta gal at the ubiquitin-beta gal junction, thereby making it possible to expose different residues at the amino-termini of the otherwise identical beta gal proteins. The beta gal proteins thus designed have strikingly different half-lives in vivo, from more than 20 hours to less than 3 minutes, depending on the nature of the amino acid at the amino-terminus of beta gal. The set of individual amino acids can thus be ordered with respect to the half-lives that they confer on beta gal when present at its amino-terminus (the "N-end rule"). The currently known amino-terminal residues in long-lived, noncompartmentalized intracellular proteins from both prokaryotes and eukaryotes belong exclusively to the stabilizing class as predicted by the N-end rule. The function of the previously described posttranslational addition of single amino acids to protein amino-termini may also be accounted for by the N-end rule. Thus the recognition of an amino-terminal residue in a protein may mediate both the metabolic stability of the protein and the potential for regulation of its stability.
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- Budding yeast Dsk2p is a polyubiquitin-binding protein that can interact with the proteasome.
- M. Funakoshi, T. Sasaki, T. Nishimoto, and H. Kobayashi (2002)
PNAS
99, 745-750
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- Construction and Analysis of Mouse Strains Lacking the Ubiquitin Ligase UBR1 (E3alpha ) of the N-End Rule Pathway.
- Y. T. Kwon, Z. Xia, I. V. Davydov, S. H. Lecker, and A. Varshavsky (2001)
Mol. Cell. Biol.
21, 8007-8021
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- Kinetic Analysis of the Conjugation of Ubiquitin to Picornavirus 3C Proteases Catalyzed by the Mammalian Ubiquitin-protein Ligase E3alpha.
- T. G. Lawson, M. E. Sweep, P. E. Schlax, R. N. Bohnsack, and A. L. Haas (2001)
J. Biol. Chem.
276, 39629-39637
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- N-end Rule Specificity within the Ubiquitin/Proteasome Pathway Is Not an Affinity Effect.
- O. V. Baboshina, R. Crinelli, T. J. Siepmann, and A. L. Haas (2001)
J. Biol. Chem.
276, 39428-39437
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- Two-hybrid analysis of the Saccharomyces cerevisiae 26S proteasome.
- G. CAGNEY, P. UETZ, and S. FIELDS (2001)
Physiol Genomics
7, 27-34
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- Upc2p and Ecm22p, Dual Regulators of Sterol Biosynthesis in Saccharomyces cerevisiae.
- A. Vik and J. Rine (2001)
Mol. Cell. Biol.
21, 6395-6405
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- Xylulokinase Overexpression in Two Strains of Saccharomyces cerevisiae Also Expressing Xylose Reductase and Xylitol Dehydrogenase and Its Effect on Fermentation of Xylose and Lignocellulosic Hydrolysate.
- B. Johansson, C. Christensson, T. Hobley, and B. Hahn-Hagerdal (2001)
Appl. Envir. Microbiol.
67, 4249-4255
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- Sequence Architecture Downstream of the Initiator Codon Enhances Gene Expression and Protein Stability in Plants.
- S. V. Sawant, K. Kiran, P. K. Singh, and R. Tuli (2001)
Plant Physiology
126, 1630-1636
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- Reconstruction of Ligand-Dependent Transactivation of Choristoneura fumiferana Ecdysone Receptor in Yeast.
- H. T. Tran, H. B. Askari, S. Shaaban, L. Price, S. R. Palli, T. S. Dhadialla, G. R. Carlson, and T. R. Butt (2001)
Mol. Endocrinol.
15, 1140-1153
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- Degradation Signals Recognized by the Ubc6p-Ubc7p Ubiquitin-Conjugating Enzyme Pair.
- T. Gilon, O. Chomsky, and R. G. Kulka (2000)
Mol. Cell. Biol.
20, 7214-7219
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- The Doa4 Deubiquitinating Enzyme Is Functionally Linked to the Vacuolar Protein-sorting and Endocytic Pathways.
- A. Y. Amerik, J. Nowak, S. Swaminathan, and M. Hochstrasser (2000)
Mol. Biol. Cell
11, 3365-3380
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- Detecting and Measuring Cotranslational Protein Degradation in.
- G. Turner and Varshavsky (2000)
Science
289, 2117-2120
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- Varying Intertrial Interval Reveals Temporally Defined Memory Deficits and Enhancements in NTAN1-Deficient Mice.
- S. A. Balogh, Y. T. Kwon, and V. H. Denenberg (2000)
Learn. Mem.
7, 279-286
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- Evidence for Separable Functions of Srp1p, the Yeast Homolog of Importin alpha (Karyopherin alpha ): Role for Srp1p and Sts1p in Protein Degradation.
- M. M. Tabb, P. Tongaonkar, L. Vu, and M. Nomura (2000)
Mol. Cell. Biol.
20, 6062-6073
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- Evidence for an Interaction between Ubiquitin-Conjugating Enzymes and the 26S Proteasome.
- P. Tongaonkar, L. Chen, D. Lambertson, B. Ko, and K. Madura (2000)
Mol. Cell. Biol.
20, 4691-4698
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- Isolation and Characterization of HRT1 Using a Genetic Screen for Mutants Unable to Degrade Gic2p in Saccharomyces cerevisiae.
- M. Blondel, J.-M. Galan, and M. Peter (2000)
Genetics
155, 1033-1044
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- Altered Activity, Social Behavior, and Spatial Memory in Mice Lacking the NTAN1p Amidase and the Asparagine Branch of the N-End Rule Pathway.
- Y. T. Kwon, S. A. Balogh, I. V. Davydov, A. S. Kashina, J. K. Yoon, Y. Xie, A. Gaur, L. Hyde, V. H. Denenberg, and A. Varshavsky (2000)
Mol. Cell. Biol.
20, 4135-4148
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- Stable High-Level Expression of Heterologous Genes In Vitro and In Vivo by Noncytopathic DNA-Based Kunjin Virus Replicon Vectors.
- A. N. Varnavski, P. R. Young, and A. A. Khromykh (2000)
J. Virol.
74, 4394-4403
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- Cytoplasmic Processing Is a Prerequisite for Presentation of an Endogenous Antigen by Major Histocompatibility Complex Class II Proteins.
- J. D. Lich, J. F. Elliott, and J. S. Blum (2000)
J. Exp. Med.
191, 1513-1524
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- Impaired Proteasome Function Rescues Thermosensitivity of Yeast Cells Lacking the Coatomer Subunit epsilon -COP.
- Y. Kimata, H. Higashio, and K. Kohno (2000)
J. Biol. Chem.
275, 10655-10660
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- Analysis of TFIIA Function In Vivo: Evidence for a Role in TATA-Binding Protein Recruitment and Gene-Specific Activation.
- Q. Liu, S. E. Gabriel, K. L. Roinick, R. D. Ward, and K. M. Arndt (1999)
Mol. Cell. Biol.
19, 8673-8685
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- Cadmium-mediated oxidative stress in kidney proximal tubule cells induces degradation of Na+/K+-ATPase through proteasomal and endo-/lysosomal proteolytic pathways.
- F. THÉVENOD and J. M. FRIEDMANN (1999)
FASEB J
13, 1751-1761
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