Cited by 859Ubiquitin and proteasome pathwaysAutophagy in Disease and TherapyProtein Structure and Dynamics

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The N-end rule: functions, mysteries, uses

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Varshavsky, A·1996·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.93.22.12142PMC PMC37957

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Abstract

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Similar but distinct versions of the N-end rule operate in all organisms examined, from mammals to fungi and bacteria. In eukaryotes, the N-end rule pathway is a part of the ubiquitin system. I discuss the mechanisms and functions of this pathway, and consider its applications.

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The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53
Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J., & Howley, P. M. (1990) · Cell · doi:10.1016/0092-8674(90)90409-8 · Cited by 3,995
A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes
Thornberry, N. A., Bull, H. G., Calaycay, J. R., Chapman, K. T., Howard, A. D., Kostura, M. J., Miller, D. K., Molineaux, S. M., Weidner, J. R., Aunins, J. G., et al. (1992) · Nature · doi:10.1038/356768a0 · Cited by 2,613
The alphaviruses: gene expression, replication, and evolution.
Strauss, J. H., & Strauss, E. G. (1994) · Microbiological Reviews · doi:10.1128/mmbr.58.3.491-562.1994 · Cited by 2,221
Mechanisms And Functions Of Cell Death
Ellis, R. E., Yuan, J., & Horvitz, H. R. (1991) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.07.110191.003311 · Cited by 2,088
In Vivo Half-Life of a Protein Is a Function of Its Amino-Terminal Residue
Bachmair, A., Finley, D. J., & Varshavsky, A. J. (1986) · Science · doi:10.1126/science.3018930 · Cited by 1,976
Self-citation
A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein
Chau, V., Tobias, J. W., Bachmair, A., Marriott, D., Ecker, D. J., Gonda, D. K., & Varshavsky, A. (1989) · Science · doi:10.1126/science.2538923 · Cited by 1,535
Self-citation
Common Principles of Protein Translocation Across Membranes
Schatz, G., & Dobberstein, B. (1996) · Science · doi:10.1126/science.271.5255.1519 · Cited by 1,116
The Human Cytomegalovirus US11 Gene Product Dislocates MHC Class I Heavy Chains from the Endoplasmic Reticulum to the Cytosol
Wiertz, E. J. H. J., Jones, T. R., Sun, L., Bogyo, M. S., Geuze, H. J., & Ploegh, H. L. (1996) · Cell · doi:10.1016/s0092-8674(00)81054-5 · Cited by 1,073
A two-component system that regulates an osmosensing MAP kinase cascade in yeast
Maeda, T., Wurgler‐Murphy, S. M., & Saito, H. (1994) · Nature · doi:10.1038/369242a0 · Cited by 1,072
Protein ubiquitination involving an E1–E2–E3 enzyme ubiquitin thioester cascade
Scheffner, M., Nuber, U. A., & Huibregtse, J. M. (1995) · Nature · doi:10.1038/373081a0 · Cited by 1,017

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[1]Lévy, F., Johnsson, N., Rümenapf, T. & Varshavsky, A. (1996) Proc. Natl. Acad. Sci. USA 93, 4907–4912.
[3]Murray, A. & Hunt, T. (1993) in The Cell Cycle (Freeman, NY), pp. 60–62.
[2]Baker, R. T. & Varshavsky, A. (1991) Proc. Natl. Acad. Sci. USA 88, 1090-1094.
[22]Dohmen, R. J., Madura, K., Bartel, B. & Varshavsky, A. (1991) Proc. Natl. Acad. Sci. USA 88, 7351–7355.
[32]Wickner, S., Gottesman, S., Skowyra, D., Hoskins, J., McKenney, K. & Maurizi, M. R. (1994) Proc. Natl. Acad. Sci. USA 91, 12218–12222.
[33]Grigoryev, S., Stewart, A. E., Kwon, Y. T., Arfin, S. M., Bradshaw, R. A., Copeland, N. J. & Varshavsky, A. (1996) J. Biol. Chem. 271, in press.
[37]Pickart, C. (1988) in Ubiquitin, ed. Rechsteiner, M. (Plenum, New York), pp. 77–99.
[43]Negrutskii, B. S. & Deutscher, M. P. (1991) Proc. Natl. Acad. Sci. USA 88, 4991-4995.
[48]Li, X. & Chang, Y. H. (1995) Proc. Natl. Acad. Sci. USA 92, 12357–12361.
[54]Scherer, D. C., Brockman, J. A., Chen, Z. J., Maniatis, T. & Ballard, D. (1995) Proc. Natl. Acad. Sci. USA 92, 11259–11263.
[58]Ota, I. M. & Varshavsky, A. (1992) Proc. Natl. Acad. Sci. USA 89, 2355–2359.
[64]Aizenman, E., Engelberg-Kulka, H. & Glaser, G. (1996) Proc. Natl. Acad. Sci. USA 93, 6059–6063.
[65]Kayalar, C., Örd, T., Testa, M. P., Zhong, L.-T. & Bredesen, D. E. (1996) Proc. Natl. Acad. Sci. USA 93, 2234–2238.
[69]Levis, M. J. & Bourne, H. R. (1992) J. Cell Biol. 119, 1297–1307. deGroot, R. J., Rümenapf, T., Kuhn, R. J., Strauss, E. G. & Strauss, J. H. (1991) Proc. Natl. Acad. Sci. USA 88, 8967–8971.
[77]Park, E. C., Finley, D. & Szostak, J. W. (1992) Proc. Natl. Acad. Sci. USA 89, 1249–1252.
[79]Varshavsky, A. (1995) Proc. Natl. Acad. Sci. USA 92, 3663–3667.

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Authors: Varshavsky, A.
Affiliations: California Institute of Technology (US)
Corresponding author: Varshavsky, A
ORCID: Varshavsky, A
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1996-10-29
Volume: 93
Issue: 22
Pages: 12142-12149
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.93.22.12142
PMC: PMC37957
OpenAlex: W1983345237
Cited by: 859
References: 77
Citations by year: 2026: 10 · 2025: 8 · 2024: 11 · 2023: 19 · 2022: 8 · 2021: 6 · 2020: 16 · 2019: 11 · 2018: 19 · 2017: 19 · 2016: 21 · 2015: 28 · 2014: 25 · 2013: 21 · 2012: 30
FWCI: 9.34
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords: N-end rule, protein half-life, N-terminal residues, ubiquitin system, protein degradation, ubiquitination, protein stability
MeSH terms: Acyltransferases, Amidohydrolases, Amino Acid Sequence, Animals, Female, Fungal Proteins, Half-Life, Ligases, Male, Models, Biological, Models, Chemical, Protein Conformation, Proteins, Rabbits, Proto-Oncogene Proteins c-mos, Evolution, Molecular, GTP-Binding Proteins, Saccharomyces cerevisiae Proteins, Ubiquitin-Protein Ligases, Mice

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