Mapping degradation signals and pathways in a eukaryotic N-terminome

• Verfasst von: Kats, Ilia [VerfasserIn]
• Verfasst von: Khmelinskii, Anton [VerfasserIn]
• Verfasst von: Kschonsak, Marc [VerfasserIn]
• Verfasst von: Huber, Florian [VerfasserIn]
• Verfasst von: Knieß, Robert A. [VerfasserIn]
• Verfasst von: Bartosik, Anna [VerfasserIn]
• Verfasst von: Knop, Michael [VerfasserIn]
• Titel: Mapping degradation signals and pathways in a eukaryotic N-terminome
• Verf.angabe: authors Ilia Kats, Anton Khmelinskii, Marc Kschonsak, Florian Huber, Robert A. Knieß, Anna Bartosik, Michael Knop
• E-Jahr: 2018
• Jahr: May 3, 2018
• Umfang: 14 S.
• Fussnoten: Gesehen am 24.05.2017
• Titel Quelle: Enthalten in: Molecular cell
• Ort Quelle: [Cambridge, Mass.] : Cell Press, 1997
• Jahr Quelle: 2018
• Band/Heft Quelle: 70(2018), 3, Seite 488-501.e5
• ISSN Quelle: 1097-4164
• DOI: doi:10.1016/j.molcel.2018.03.033
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Forschungsdaten: Kats, Ilia: Mapping degradation signals and pathways in a eukaryotic N-terminome [data set]
• Sach-SW: deep sequencing
• Sach-SW: massively parallel protein turnover assays
• Sach-SW: multiplexed protein stability profiling
• Sach-SW: N-end rule
• Sach-SW: N-terminal acetylation
• Sach-SW: N-terminal methionine excision
• Sach-SW: N-terminal processing
• Sach-SW: protein quality control
• Sach-SW: selective protein degradation
• K10plus-PPN: 1575491036

Abstract

Summary: Most eukaryotic proteins are N-terminally acetylated. This modification can be recognized as a signal for selective protein degradation (degron) by the N-end rule pathways. However, the prevalence and specificity of such degrons in the proteome are unclear. Here, by systematically examining how protein turnover is affected by N-terminal sequences, we perform a comprehensive survey of degrons in the yeast N-terminome. We find that approximately 26% of nascent protein N termini encode cryptic degrons. These degrons exhibit high hydrophobicity and are frequently recognized by the E3 ubiquitin ligase Doa10, suggesting a role in protein quality control. In contrast, N-terminal acetylation rarely functions as a degron. Surprisingly, we identify two pathways where N-terminal acetylation has the opposite function and blocks protein degradation through the E3 ubiquitin ligase Ubr1. Our analysis highlights the complexity of N-terminal degrons and argues that hydrophobicity, not N-terminal acetylation, is the predominant feature of N-terminal degrons in nascent proteins.