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

An ubiquitin-binding molecule can work as an inhibitor of ubiquitin processing enzymes and ubiquitin receptors
An ubiquitin-binding molecule can work as an inhibitor of ubiquitin processing enzymes and ubiquitin receptors
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 ?-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.
0006-291X
33-39
Nguyen, Thanh
f71be1c4-c647-4229-bb13-d8dc90d5e527
Ho, Min
d35bf21f-50be-42dd-8914-29ece70c86be
Ghosh, Ambarnil
fc9ce7bb-daa2-49e9-a7d6-813a8b1aa6a9
Kim, Truc
64fff945-d3dc-4145-b714-d76a7024b786
Yun, Sun Il
de6b49a3-c4df-4397-af27-6b1e93a69eb4
Lee, Seung Seo
ee34fa26-5fb6-48c8-80c2-1f13ec4ccceb
Kim, Kyeong Kyu
a7757cb7-065e-4e76-a669-27d2108bef97
Nguyen, Thanh
f71be1c4-c647-4229-bb13-d8dc90d5e527
Ho, Min
d35bf21f-50be-42dd-8914-29ece70c86be
Ghosh, Ambarnil
fc9ce7bb-daa2-49e9-a7d6-813a8b1aa6a9
Kim, Truc
64fff945-d3dc-4145-b714-d76a7024b786
Yun, Sun Il
de6b49a3-c4df-4397-af27-6b1e93a69eb4
Lee, Seung Seo
ee34fa26-5fb6-48c8-80c2-1f13ec4ccceb
Kim, Kyeong Kyu
a7757cb7-065e-4e76-a669-27d2108bef97

Nguyen, Thanh, Ho, Min, Ghosh, Ambarnil, Kim, Truc, Yun, Sun Il, Lee, Seung Seo and Kim, Kyeong Kyu (2016) An ubiquitin-binding molecule can work as an inhibitor of ubiquitin processing enzymes and ubiquitin receptors. Biochemical and Biophysical Research Communications, 479 (1), 33-39. (doi:10.1016/j.bbrc.2016.09.010). (PMID:27613091)

Record type: Article

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 ?-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.

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More information

Accepted/In Press date: 2 September 2016
e-pub ahead of print date: 7 September 2016
Published date: 7 October 2016

Identifiers

Local EPrints ID: 400879
URI: http://eprints.soton.ac.uk/id/eprint/400879
ISSN: 0006-291X
PURE UUID: f1f7ca93-bc23-4e93-915f-f78ea5a261c7
ORCID for Seung Seo Lee: ORCID iD orcid.org/0000-0002-8598-3303

Catalogue record

Date deposited: 28 Sep 2016 15:40
Last modified: 07 Oct 2020 04:37

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