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Please use this identifier to cite or link to this item: http://hdl.handle.net/10373/251

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Title: Bioluminescent imaging of Cdk2 inhibition in vivo
Authors: Zhang, Guo-Jun
Safran, Michal
Wei, Wenyi
Sorensen, Erik
Lassota, Peter
Zhelev, Nikolai Z.
Neuberg, Donna S.
Shapiro, Geoffrey
Kaelin Jr, William G.
Affiliation: University of Abertay Dundee. School of Social and Health Sciences
Keywords: Cyclin-dependent kinases
Issue Date: May-2004
Publisher: Nature Publishing Group
Type: Journal Article
Refereed: peer-reviewed
Rights: Published version (c)Nature Publishing Group, available from DOI: 10.1038/nm1047
Citation: Zhang, G., et al. 2004. Bioluminescent imaging of Cdk2 inhibition in vivo. Nature Medicine. 10(6): pp.643-648. [Online] Available from: DOI: 10.1038/nm1047
Abstract: Many proteins and pathways of pharmaceutical interest impinge on ubiquitin ligases or their substrates. The cyclin-dependent kinase (Cdk) inhibitor p27, for example, is polyubiquitylated in a cell cycle−dependent manner by a ubiquitin ligase complex containing the F-box protein Skp2. Regulated turnover of p27 is due, at least partly, to its phosphorylation by Cdk2 on threonine 187, which generates a Skp2-binding site. We made a p27-luciferase (p27Luc) fusion protein and show here that its abundance, like that of p27, is regulated by Skp2 in a cell cycle−dependent manner. As predicted, p27Luc levels increased after blocking Cdk2 activity with inhibitory proteins, peptides or small interfering RNA (siRNA). Accumulation of p27Luc in response to Cdk2 inhibitory drugs (flavopiridol and R-roscovitine) was demonstrable in human tumor cells in vivo using noninvasive bioluminescent imaging. In theory, the approach described here could be used to develop bioluminescent reporters for any drug target that directly or indirectly affects the turnover of a ubiquitin ligase substrate.
URI: http://hdl.handle.net/10373/251
ISSN: 1078-8956
Appears in Collections:Social & Health Sciences Collection

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