期刊
BIOMOLECULES
卷 11, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/biom11030482
关键词
neddylation; NEDD8; Dictyostelium discoideum; social amoeba; MLN4924; post-translational modification; growth; chemotaxis; development
资金
- Natural Sciences and Engineering Research Council of Canada [RGPIN-2018-04855]
- Killam Pre-Doctoral Award from Dalhousie University
- Nova Scotia Graduate Scholarship from Dalhousie University
- Dalhousie University
Neddylation is a crucial post-translational modification that influences cell growth and development processes. In the social amoeba Dictyostelium discoideum, the impact of neddylation is demonstrated through the use of the inhibitor MLN4924.
Neddylation is a post-translational modification that is essential for a variety of cellular processes and is linked to many human diseases including cancer, neurodegeneration, and autoimmune disorders. Neddylation involves the conjugation of the ubiquitin-like modifier neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) to target proteins, and has been studied extensively in various eukaryotes including fungi, plants, and metazoans. Here, we examine the biological processes influenced by neddylation in the social amoeba, Dictyostelium discoideum, using a well-established inhibitor of neddylation, MLN4924 (pevonedistat). NEDD8, and the target of MLN4924 inhibition, NEDD8-activating enzyme E1 (NAE1), are highly conserved in D. discoideum (Nedd8 and Nae1, respectively). Treatment of D. discoideum cells with MLN4924 increased the amount of free Nedd8, suggesting that MLN4924 inhibited neddylation. During growth, MLN4924 suppressed cell proliferation and folic acid-mediated chemotaxis. During multicellular development, MLN4924 inhibited cyclic adenosine monophosphate (cAMP)-mediated chemotaxis, delayed aggregation, and suppressed fruiting body formation. Together, these findings indicate that neddylation plays an important role in regulating cellular and developmental events during the D. discoideum life cycle and that this organism can be used as a model system to better understand the essential roles of neddylation in eukaryotes, and consequently, its involvement in human disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据