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N-degron pathways
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2024-09-12 , DOI: 10.1073/pnas.2408697121 Alexander Varshavsky 1
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2024-09-12 , DOI: 10.1073/pnas.2408697121 Alexander Varshavsky 1
Affiliation
An N-degron is a degradation signal whose main determinant is a “destabilizing” N-terminal residue of a protein. Specific N-degrons, discovered in 1986, were the first identified degradation signals in short-lived intracellular proteins. These N-degrons are recognized by a ubiquitin-dependent proteolytic system called the Arg/N-degron pathway. Although bacteria lack the ubiquitin system, they also have N-degron pathways. Studies after 1986 have shown that all 20 amino acids of the genetic code can act, in specific sequence contexts, as destabilizing N-terminal residues. Eukaryotic proteins are targeted for the conditional or constitutive degradation by at least five N-degron systems that differ both functionally and mechanistically: the Arg/N-degron pathway, the Ac/N-degron pathway, the Pro/N-degron pathway, the fMet/N-degron pathway, and the newly named, in this perspective, GASTC/N-degron pathway (GASTC = Gly, Ala, Ser, Thr, Cys). I discuss these systems and the expanded terminology that now encompasses the entire gamut of known N-degron pathways.
中文翻译:
N-降解决定子途径
N-降解决定子是一种降解信号,其主要决定因素是蛋白质的“不稳定”N-末端残基。 1986 年发现的特定 N 降解决定子是第一个在短寿命细胞内蛋白质中发现的降解信号。这些 N-降解决定子被泛素依赖性蛋白水解系统(称为 Arg/N-降解决定子途径)识别。尽管细菌缺乏泛素系统,但它们也具有 N-降解决定子途径。 1986 年之后的研究表明,遗传密码的所有 20 个氨基酸在特定的序列背景下都可以充当不稳定的 N 末端残基。真核蛋白被至少五个在功能和机制上都不同的 N-降解决定子系统进行条件性或组成性降解:Arg/N-降解决定子途径、Ac/N-降解决定子途径、Pro/N-降解决定子途径、 fMet/N-degron 途径,从这个角度来看,新命名为 GASTC/N-degron 途径(GASTC = Gly、Ala、Ser、Thr、Cys)。我讨论了这些系统和扩展的术语,这些术语现在涵盖了已知 N-降解决定子通路的整个范围。
更新日期:2024-09-12
中文翻译:
N-降解决定子途径
N-降解决定子是一种降解信号,其主要决定因素是蛋白质的“不稳定”N-末端残基。 1986 年发现的特定 N 降解决定子是第一个在短寿命细胞内蛋白质中发现的降解信号。这些 N-降解决定子被泛素依赖性蛋白水解系统(称为 Arg/N-降解决定子途径)识别。尽管细菌缺乏泛素系统,但它们也具有 N-降解决定子途径。 1986 年之后的研究表明,遗传密码的所有 20 个氨基酸在特定的序列背景下都可以充当不稳定的 N 末端残基。真核蛋白被至少五个在功能和机制上都不同的 N-降解决定子系统进行条件性或组成性降解:Arg/N-降解决定子途径、Ac/N-降解决定子途径、Pro/N-降解决定子途径、 fMet/N-degron 途径,从这个角度来看,新命名为 GASTC/N-degron 途径(GASTC = Gly、Ala、Ser、Thr、Cys)。我讨论了这些系统和扩展的术语,这些术语现在涵盖了已知 N-降解决定子通路的整个范围。