dictyNews
Electronic Edition
Volume 47, number 7
March 19, 2021
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Abstracts
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nhibiting neddylation with MLN4924 suppresses growth and delays
multicellular development in Dictyostelium discoideum
Robert J. Huber 1, William D. Kim 2 , Sabateeshan Mathavarajah 3
1. Department of Biology, Trent University, Peterborough,
Ontario, Canada; [log in to unmask]
2. Environmental and Life Sciences Graduate Program, Trent
University, Peterborough, Ontario, Canada; [log in to unmask]
3. Department of Pathology, Dalhousie University, Halifax,
Nova Scotia, Canada; [log in to unmask]
Biomolecules, accepted
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
diseases. 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 examined the biological processes
influenced by neddylation in the social amoeba, Dictyostelium
discoideum, using a well-established inhibitor of neddylation,
MLN4924 (Pevonedistat). The target of MLN4924 inhibition, NAE1,
is highly conserved in D.discoideum. Treatment of D.discoideum
cells with MLN4924 increased the amount of free Nedd8 suggesting
that treatment inhibited neddylation. During growth, MLN4924
suppressed cell proliferation and folic acid-mediated chemotaxis.
During multicellular development, MLN4924 inhibited 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.
submitted by: Robert Huber [[log in to unmask]]
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