A Generic Platform for Cellular Screening Against Ubiquitin Ligases

Timurs Maculins, Nikki Carter, Thierry Dorval, Kevin Hudson, J. Willem M Nissink, Ronald T. Hay, Husam Alwan (Lead / Corresponding author)

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Abstract

Ubiquitin signalling regulates most aspects of cellular life, thus deregulation of ubiquitylation has been linked with a number of diseases. E3 ubiquitin ligases provide substrate selectivity in ubiquitylation cascades and are therefore considered to be attractive targets for developing therapeutic molecules. In contrast to established drug target classes, such as protein kinases, GPCRs, hormone receptors and ion channels, ubiquitin drug discovery is in its early stages. This is, in part, due to the complexity of the ubiquitylation pathways and the lack of robust quantitative technologies that allow high-throughput screening of inhibitors. Here we report the development of a Ubiquitin Ligase Profiling system, which is a novel and generic cellular technology designed to facilitate identification of selective inhibitors against RING type E3 ubiquitin ligases. Utilization of this system requires a single co-transfection of cells with assay vectors, thereby enabling readout of E3 ubiquitin ligase catalytic activity within the cellular environment. Therefore, our robust high-throughput screening platform offers novel opportunities for the development of inhibitors against this difficult-to-target E3 ligase enzyme class.

Original languageEnglish
Article number18940
JournalScientific Reports
Volume6
Early online date8 Jan 2016
DOIs
Publication statusPublished - 8 Jan 2016

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Ubiquitin-Protein Ligases
Ligases
Ubiquitin
Ubiquitination
Technology
Drug Discovery
Ion Channels
Protein Kinases
Transfection
Hormones
Enzymes
Pharmaceutical Preparations
Therapeutics

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Maculins, T., Carter, N., Dorval, T., Hudson, K., Nissink, J. W. M., Hay, R. T., & Alwan, H. (2016). A Generic Platform for Cellular Screening Against Ubiquitin Ligases. Scientific Reports, 6, [18940]. https://doi.org/10.1038/srep18940
Maculins, Timurs ; Carter, Nikki ; Dorval, Thierry ; Hudson, Kevin ; Nissink, J. Willem M ; Hay, Ronald T. ; Alwan, Husam. / A Generic Platform for Cellular Screening Against Ubiquitin Ligases. In: Scientific Reports. 2016 ; Vol. 6.
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Maculins, T, Carter, N, Dorval, T, Hudson, K, Nissink, JWM, Hay, RT & Alwan, H 2016, 'A Generic Platform for Cellular Screening Against Ubiquitin Ligases', Scientific Reports, vol. 6, 18940. https://doi.org/10.1038/srep18940

A Generic Platform for Cellular Screening Against Ubiquitin Ligases. / Maculins, Timurs; Carter, Nikki; Dorval, Thierry; Hudson, Kevin; Nissink, J. Willem M; Hay, Ronald T.; Alwan, Husam (Lead / Corresponding author).

In: Scientific Reports, Vol. 6, 18940, 08.01.2016.

Research output: Contribution to journalArticle

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Maculins T, Carter N, Dorval T, Hudson K, Nissink JWM, Hay RT et al. A Generic Platform for Cellular Screening Against Ubiquitin Ligases. Scientific Reports. 2016 Jan 8;6. 18940. https://doi.org/10.1038/srep18940