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The N-end Rule

Varshavsky, A. J. (1995) The N-end Rule. Cold Spring Harbor Symposia on Quantitative Biology, 60 . pp. 461-478. ISSN 0091-7451. doi:10.1101/sqb.1995.060.01.051.

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The N-end rule relates the in vivo half-life1 of a protein to the identity of its N-terminal residue (Varshavsky 1992). Similar but distinct versions of the N-end rule have been shown to operate in all organisms examined, from mammals to fungi and bacteria. I summarize the current understanding of the N-end rule pathway and describe some of the recent methods that utilize the N-end rule. Features of a protein that confer metabolic instability are called degradation signals, or degrons (Varshavsky 1991). The essential component of one degron, the first to be identified, is a destabilizing N-terminal residue of a protein (Bachmair et al. 1986). This signal is called the N-degron. The N-end rule (defined above) results from the existence of N-degrons containing different destabilizing residues (Varshavsky 1992). In eukaryotes, the N-degron comprises two determinants: a destabilizing N-terminal residue and an internal lysine (or lysines) of a substrate. The lysine residue is the site of formation of a multiubiquitin chain, which is required for the degradation of at least some N-end rule substrates (Bachmair and Varshavsky 1989; Hill et al. 1993; Dohmen et al. 1994). Ubiquitin (Ub) is a 76-residue protein whose covalent conjugation to other proteins (often in the form of a multi-Ub chain) plays a role in a number of processes, primarily through routes that involve protein degradation (for review, see Finley and Chau 1991; Gottesman and Maurizi 1992; Hershko and Ciechanover 1992; Jentsch 1992; Varshavsky 1992, 1995a; Parsell and Lindquist 1993; Vierstra 1993; Ciechanover 1994; Gonda 1994; Hochstrasser 1995).

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Varshavsky, A. J.0000-0002-4011-258X
Additional Information:© 1995 by Cold Spring Harbor Laboratory Press. This paper is dedicated to the memory of Harold Weintraub (1945-1995)--a remarkable scientist and man of uncommon goodness. I am grateful to the current and former members of the laboratory whose work on the N-end rule is discussed above. I also thank C. Byrd, M. Ghislain, Y.-T. Kwon, F. Lévy, and especially G. Turner for comments on the manuscript.
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Official Citation:The N-end Rule. A. Varshavsky. Cold Spring Harb Symp Quant Biol 1995 60: 461-478; doi:10.1101/SQB.1995.060.01.051
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108019
Deposited By: George Porter
Deposited On:12 Feb 2021 16:02
Last Modified:16 Nov 2021 19:08

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