Mapping degradation signals and pathways in a eukaryotic N-terminome / authors Ilia Kats, Anton Khmelinskii, Marc Kschonsak, Florian Huber, Robert A. Knieß, Anna Bartosik, Michael Knop

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.

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Persons: Kats, Ilia [Author]; Khmelinskii, Anton [Author]; Kschonsak, Marc [Author]; Huber, Florian [Author]; Knieß, Robert A. [Author]; Bartosik, Anna [Author]; Knop, Michael [Author]
Format: eArticle
Language(s):English
Publication:May 3, 2018
Part of:Molecular cell 70(2018), 3, Seite 488-501.e5
Subjects:deep sequencing
massively parallel protein turnover assays
multiplexed protein stability profiling
N-end rule
N-terminal acetylation
N-terminal methionine excision
N-terminal processing
protein quality control
selective protein degradation
Related resources:Forschungsdaten: Mapping degradation signals and pathways in a eukaryotic N-terminome [data set]
Notes:Gesehen am 24.05.2017
Physical description:14
ISSN:1097-4164
DOI:10.1016/j.molcel.2018.03.033