PuSH - Publication Server of Helmholtz Zentrum München

Vogl, A.M.* ; Phu, L.* ; Becerra, R.* ; Giusti, S.A.* ; Verschueren, E.* ; Hinkle, T.B.* ; Bordenave, M.D.* ; Adrian, M.* ; Heidersbach, A.* ; Yankilevich, P.* ; Stefani, F.D.* ; Wurst, W. ; Hoogenraad, C.C.* ; Kirkpatrick, D.S.* ; Refojo, D.* ; Sheng, M.*

Global site-specific neddylation profiling reveals that NEDDylated cofilin regulates actin dynamics.

Nat. Struct. Mol. Biol. 27, 210-220 (2020)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Neddylation is the post-translational protein modification most closely related to ubiquitination. Whereas the ubiquitin-like protein NEDD8 is well studied for its role in activating cullin−RING E3 ubiquitin ligases, little is known about other substrates. We developed serial NEDD8-ubiquitin substrate profiling (sNUSP), a method that employs NEDD8 R74K knock-in HEK293 cells, allowing discrimination of endogenous NEDD8- and ubiquitin-modification sites by MS after Lys-C digestion and K-εGG-peptide enrichment. Using sNUSP, we identified 607 neddylation sites dynamically regulated by the neddylation inhibitor MLN4924 and the de-neddylating enzyme NEDP1, implying that many non-cullin proteins are neddylated. Among the candidates, we characterized lysine 112 of the actin regulator cofilin as a novel neddylation event. Global inhibition of neddylation in developing neurons leads to cytoskeletal defects, altered actin dynamics and neurite growth impairments, whereas site-specific neddylation of cofilin at K112 regulates neurite outgrowth, suggesting that cofilin neddylation contributes to the regulation of neuronal actin organization.
Altmetric
Additional Metrics?
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Quellenangaben Volume: 27, Issue: 2, Pages: 210-220 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed