N- degron pathways

• 成果类型: Article
• 署名作者: Varshavsky, Alexander
• 署名单位: California Institute of Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13665
• DOI: 10.1073/pnas.2408697121
• 发表日期: 2024-09-24
• 关键词: end rule pathway; ubiquitin-proteasome system; terminal acetylation; protein modification; degradation signal; cellular-proteins; ligase; RECOGNITION; specificity; methionine

摘要

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/ 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.