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Biochem Biophys Res Commun. 2016 Oct 7;479(1):33-9. doi: 10.1016/j.bbrc.2016.09.010. Epub 2016 Sep 7.

An ubiquitin-binding molecule can work as an inhibitor of ubiquitin processing enzymes and ubiquitin receptors.

Author information

1
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 440-746, South Korea.
2
Department of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK. Electronic address: S.S.Lee@soton.ac.uk.
3
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 440-746, South Korea. Electronic address: kyeongkyu@skku.edu.

Abstract

The ubiquitin pathway plays a critical role in regulating diverse biological processes, and its dysregulation is associated with various diseases. Therefore, it is important to have a tool that can control the ubiquitin pathway in order to improve understanding of this pathway and to develop therapeutics against relevant diseases. We found that Chicago Sky Blue 6B binds directly to the β-groove, a major interacting surface of ubiquitin. Hence, it could successfully inhibit the enzymatic activity of ubiquitin processing enzymes and the binding of ubiquitin to the CXCR4, a cell surface ubiquitin receptor. Furthermore, we demonstrated that this ubiquitin binding chemical could effectively suppress the ubiquitin induced cancer cell migration by blocking ubiquitin-CXCR4 interaction. Current results suggest that ubiquitin binding molecules can be developed as inhibitors of ubiquitin-protein interactions, which will have the value not only in unveiling the biological role of ubiquitin but also in treating related diseases.

KEYWORDS:

CXC4 antagonist; Chicago sky blue 6B; Druggable target; Protein-protein interaction; Ubiquitin; Ubiquitin inhibitor

PMID:
27613091
DOI:
10.1016/j.bbrc.2016.09.010
[Indexed for MEDLINE]

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