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

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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Crossref · 10.1073/pnas.93.22.12142

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  • The N-end rule and the SsrA tag are the best characterized mechanisms by which bacterial proteases recognize substrates.

    “Currently, the most well characterized mechanisms for substrate recognition by bacterial proteases are the N-end rule and the SsrA tag.”

    From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [54]

  • The N-end rule ties a protein's half-life to its N-terminal amino acid.

    “The N-end rule relates the half-life of a protein to the N-terminal amino acid while the SsrA tag is an eleven amino acid tag that is added to the carboxy-terminus of incompletely translated proteins relegating them to degradation [54–55].”

    From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [54]

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Research works printed but not linked: 16

  1. [1]Lévy, F., Johnsson, N., Rümenapf, T. & Varshavsky, A. (1996) Proc. Natl. Acad. Sci. USA 93, 4907–4912.
  2. [3]Murray, A. & Hunt, T. (1993) in The Cell Cycle (Freeman, NY), pp. 60–62.
  3. [2]Baker, R. T. & Varshavsky, A. (1991) Proc. Natl. Acad. Sci. USA 88, 1090-1094.
  4. [22]Dohmen, R. J., Madura, K., Bartel, B. & Varshavsky, A. (1991) Proc. Natl. Acad. Sci. USA 88, 7351–7355.
  5. [32]Wickner, S., Gottesman, S., Skowyra, D., Hoskins, J., McKenney, K. & Maurizi, M. R. (1994) Proc. Natl. Acad. Sci. USA 91, 12218–12222.
  6. [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.
  7. [37]Pickart, C. (1988) in Ubiquitin, ed. Rechsteiner, M. (Plenum, New York), pp. 77–99.
  8. [43]Negrutskii, B. S. & Deutscher, M. P. (1991) Proc. Natl. Acad. Sci. USA 88, 4991-4995.
  9. [48]Li, X. & Chang, Y. H. (1995) Proc. Natl. Acad. Sci. USA 92, 12357–12361.
  10. [54]Scherer, D. C., Brockman, J. A., Chen, Z. J., Maniatis, T. & Ballard, D. (1995) Proc. Natl. Acad. Sci. USA 92, 11259–11263.
  11. [58]Ota, I. M. & Varshavsky, A. (1992) Proc. Natl. Acad. Sci. USA 89, 2355–2359.
  12. [64]Aizenman, E., Engelberg-Kulka, H. & Glaser, G. (1996) Proc. Natl. Acad. Sci. USA 93, 6059–6063.
  13. [65]Kayalar, C., Örd, T., Testa, M. P., Zhong, L.-T. & Bredesen, D. E. (1996) Proc. Natl. Acad. Sci. USA 93, 2234–2238.
  14. [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.
  15. [77]Park, E. C., Finley, D. & Szostak, J. W. (1992) Proc. Natl. Acad. Sci. USA 89, 1249–1252.
  16. [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
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
  • Health Sciences › Medicine › Epidemiology › 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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