The N-End rule pathway

Takafumi Tasaki, Shashikanth M. Sriram, Kyong Soo Park, Yongtae Kwon

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

The N-end rule pathway is a proteolytic system in which N-terminal residues of short-lived proteins are recognized by recognition components (N-recognins) as essential components of degrons, called N-degrons. Known N-recognins in eukaryotes mediate protein ubiquitylation and selective proteolysis by the 26S proteasome. Substrates of N-recognins can be generated when normally embedded destabilizing residues are exposed at the N terminus by proteolytic cleavage. N-degrons can also be generated through modifications of posttranslationally exposed pro-N-degrons of otherwise stable proteins; such modifications include oxidation, arginylation, leucylation, phenylalanylation, and acetylation. Although there are variations in components, degrons, and hierarchical structures, the proteolytic systems based on generation and recognition of N-degrons have been observed in all eukaryotes and prokaryotes examined thus far. The N-end rule pathway regulates homeostasis of various physiological processes, in part, through interaction with small molecules. Here, we review the biochemical mechanisms, structures, physiological functions, and small-molecule-mediated regulation of the N-end rule pathway.

Original languageEnglish
Pages (from-to)261-289
Number of pages29
JournalAnnual Review of Biochemistry
Volume81
DOIs
StatePublished - 1 Jul 2012

Fingerprint

Eukaryota
Proteolysis
Physiological Phenomena
Acetylation
Proteins
Molecules
Ubiquitination
Homeostasis
Oxidation
Substrates
recognins
ATP dependent 26S protease

Keywords

  • N-degron
  • arginylation
  • proteolysis
  • ubiquitin

Cite this

Tasaki, Takafumi ; Sriram, Shashikanth M. ; Park, Kyong Soo ; Kwon, Yongtae. / The N-End rule pathway. In: Annual Review of Biochemistry. 2012 ; Vol. 81. pp. 261-289.
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The N-End rule pathway. / Tasaki, Takafumi; Sriram, Shashikanth M.; Park, Kyong Soo; Kwon, Yongtae.

In: Annual Review of Biochemistry, Vol. 81, 01.07.2012, p. 261-289.

Research output: Contribution to journalArticle

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