[分享]活体成像技术关于抗肿瘤药物研究的一篇文献（Nat Med）

Bioluminescent imaging of Cdk2 inhibition in vivo.
Nat Med. 2004 Jun;10(6):643-8. Epub 2004 May 2.

Zhang GJ, Safran M, Wei W, Sorensen E, Lassota P, Zhelev N, Neuberg DS, Shapiro G, Kaelin WG Jr.

Department of Adult Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.


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.

OK

全文已经上传

相关附件

谢谢。我不知道如何上传文件？我有很多文献。

好好好