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Article

Inhibiting Neddylation with MLN4924 Suppresses Growth and Delays Multicellular Development in Dictyostelium discoideum

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Department of Biology, Trent University, Peterborough, ON K9L 0G2, Canada
2
Environmental and Life Sciences Graduate Program, Trent University, Peterborough, ON K9L 0G2, Canada
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Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Dmitris Xirodimas
Biomolecules 2021, 11(3), 482; https://doi.org/10.3390/biom11030482
Received: 12 February 2021 / Revised: 17 March 2021 / Accepted: 19 March 2021 / Published: 23 March 2021
(This article belongs to the Special Issue Looking Back and Ahead: Emerging Concepts in Ubiquitin and UBLs)
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. View Full-Text
Keywords: neddylation; NEDD8; Dictyostelium discoideum; social amoeba; MLN4924; post-translational modification; growth; chemotaxis; development neddylation; NEDD8; Dictyostelium discoideum; social amoeba; MLN4924; post-translational modification; growth; chemotaxis; development
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MDPI and ACS Style

Huber, R.J.; Kim, W.D.; Mathavarajah, S. Inhibiting Neddylation with MLN4924 Suppresses Growth and Delays Multicellular Development in Dictyostelium discoideum. Biomolecules 2021, 11, 482. https://doi.org/10.3390/biom11030482

AMA Style

Huber RJ, Kim WD, Mathavarajah S. Inhibiting Neddylation with MLN4924 Suppresses Growth and Delays Multicellular Development in Dictyostelium discoideum. Biomolecules. 2021; 11(3):482. https://doi.org/10.3390/biom11030482

Chicago/Turabian Style

Huber, Robert J., William D. Kim, and Sabateeshan Mathavarajah. 2021. "Inhibiting Neddylation with MLN4924 Suppresses Growth and Delays Multicellular Development in Dictyostelium discoideum" Biomolecules 11, no. 3: 482. https://doi.org/10.3390/biom11030482

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