Ubiquitination of the Dishevelled DIX domain blocks its head-to-tail polymerization

Julia Madrzak, Marc Fiedler, Christopher M. Johnson, Richard Ewan, Axel Knebel, Mariann Bienz () and Jason W. Chin ()
Additional contact information
Julia Madrzak: MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue
Marc Fiedler: MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue
Christopher M. Johnson: MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue
Richard Ewan: MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee
Axel Knebel: MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee
Mariann Bienz: MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue
Jason W. Chin: MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Dishevelled relays Wnt signals from the plasma membrane to different cytoplasmic effectors. Its signalling activity depends on its DIX domain, which undergoes head-to-tail polymerization to assemble signalosomes. The DIX domain is ubiquitinated in vivo at multiple lysines, which can be antagonized by various deubiquitinases (DUBs) including the CYLD tumour suppressor that attenuates Wnt signalling. Here, we generate milligram quantities of pure human Dvl2 DIX domain mono-ubiquitinated at two lysines (K54 and K58) by genetically encoded orthogonal protection with activated ligation (GOPAL), to investigate their effect on DIX polymerization. We show that the ubiquitination of DIX at K54 blocks its polymerization in solution, whereas DIX58-Ub remains oligomerization-competent. DUB profiling identified 28 DUBs that cleave DIX-ubiquitin conjugates, half of which prefer, or are specific for, DIX54-Ub, including Cezanne and CYLD. These DUBs thus have the potential to promote Dvl polymerization and signalosome formation, rather than antagonize it as previously thought for CYLD.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms7718 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7718

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms7718

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().