线性多泛素重塑了果蝇的蛋白质组,并影响了数百种调节因子。

IF 2.1 3区 生物学 Q3 GENETICS & HEREDITY G3: Genes|Genomes|Genetics Pub Date : 2024-11-06 DOI:10.1093/g3journal/jkae209
Oluwademilade Nuga, Kristin Richardson, Nikhil C Patel, Xusheng Wang, Vishwajeeth Pagala, Anna Stephan, Junmin Peng, Fabio Demontis, Sokol V Todi
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引用次数: 0

摘要

泛素通过与底物的翻译后连接控制许多细胞过程。由于它能够形成具有各种拓扑结构的多泛素链,因此其用途非常多变。其中,线性链已成为免疫反应和蛋白质降解的重要调节因子。以前在黑腹果蝇中进行的研究发现,表达无法分解成单个分子的线性多泛素会导致其泛素化和降解,或者导致其与蛋白质结合。然而,哪些蛋白质对线性多泛素敏感仍然是个未知数。为了解决这个问题,我们扩展了工具包以调节线性链,并对表达由 2、4 或 6 个分子组成的不可清除的线性链的苍蝇进行了超深度覆盖蛋白质组学研究。我们发现,这些链通过影响数百种蛋白质(如昼夜节律因子隐色素)来调控果蝇体内共同的和不同的细胞过程。我们的研究结果为我们深入了解受不同长度的线性多泛素链影响的蛋白质组子集和细胞通路提供了重要信息,并表明泛素系统具有极高的柔韧性。
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Linear poly-ubiquitin remodels the proteome and influences hundreds of regulators in Drosophila.

Ubiquitin controls many cellular processes via its posttranslational conjugation onto substrates. Its use is highly variable due to its ability to form poly-ubiquitin chains with various topologies. Among them, linear chains have emerged as important regulators of immune responses and protein degradation. Previous studies in Drosophila melanogaster found that expression of linear poly-ubiquitin that cannot be dismantled into single moieties leads to their ubiquitination and degradation or, alternatively, to their conjugation onto proteins. However, it remains largely unknown which proteins are sensitive to linear poly-ubiquitin. To address this question, here we expanded the toolkit to modulate linear chains and conducted ultra-deep coverage proteomics from flies that express noncleavable, linear chains comprising 2, 4, or 6 moieties. We found that these chains regulate shared and distinct cellular processes in Drosophila by impacting hundreds of proteins, such as the circadian factor Cryptochrome. Our results provide key insight into the proteome subsets and cellular pathways that are influenced by linear poly-ubiquitin chains with distinct lengths and suggest that the ubiquitin system is exceedingly pliable.

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来源期刊
G3: Genes|Genomes|Genetics
G3: Genes|Genomes|Genetics GENETICS & HEREDITY-
CiteScore
5.10
自引率
3.80%
发文量
305
审稿时长
3-8 weeks
期刊介绍: G3: Genes, Genomes, Genetics provides a forum for the publication of high‐quality foundational research, particularly research that generates useful genetic and genomic information such as genome maps, single gene studies, genome‐wide association and QTL studies, as well as genome reports, mutant screens, and advances in methods and technology. The Editorial Board of G3 believes that rapid dissemination of these data is the necessary foundation for analysis that leads to mechanistic insights. G3, published by the Genetics Society of America, meets the critical and growing need of the genetics community for rapid review and publication of important results in all areas of genetics. G3 offers the opportunity to publish the puzzling finding or to present unpublished results that may not have been submitted for review and publication due to a perceived lack of a potential high-impact finding. G3 has earned the DOAJ Seal, which is a mark of certification for open access journals, awarded by DOAJ to journals that achieve a high level of openness, adhere to Best Practice and high publishing standards.
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