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Identification of a novel Polo-like kinase 1 inhibitor that specifically blocks the functions of Polo-Box domain.

Title: Identification of a novel Polo-like kinase 1 inhibitor that specifically blocks the functions of Polo-Box domain.
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Name(s): Chen, Yunyu, author
Zhang, Jing, author
Li, Dongsheng, author
Jiang, Jiandong, author
Wang, Yanchang, author
Si, Shuyi, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2017-01-03
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Polo-like kinase 1 (Plk1) is a promising target for cancer therapy due to its essential role in cell division. In addition to a highly conserved kinase domain, Plk1 also contains a Polo-Box domain (PBD), which is essential for Plk1's subcellular localization and mitotic functions. We adopted a fluorescence polarization assay and identified a new Plk1 PBD inhibitor T521 from a small-molecule compound library. T521 specifically inhibits the PBD of Plk1, but not those of Plk2-3. T521 exhibits covalent binding to some lysine residues of Plk1 PBD, which causes significant changes in the secondary structure of Plk1 PBD. Using a cell-based assay, we showed that T521 impedes the interaction between Plk1 and Bub1, a mitotic checkpoint protein. Moreover, HeLa cells treated with T521 exhibited dramatic mitotic defects. Importantly, T521 suppresses the growth of A549 cells in xenograft nude mice. Taken together, we have identified a novel Plk1 inhibitor that specifically disrupts the functions of Plk1 PBD and shows anticancer activity.
Identifier: FSU_pmch_27902479 (IID), 10.18632/oncotarget.13603 (DOI), PMC5352051 (PMCID), 27902479 (RID), 27902479 (EID), 13603 (PII)
Keywords: Polo-Box domain, Polo-like kinase 1 inhibitor, Cancer therapy, Fluorescence polarization, Protein-protein interactions
Grant Number: R01 GM102115
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352051.
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_27902479
Owner Institution: FSU
Is Part Of: Oncotarget.
1949-2553
Issue: iss. 1, vol. 8

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Chen, Y., Zhang, J., Li, D., Jiang, J., Wang, Y., & Si, S. (2017). Identification of a novel Polo-like kinase 1 inhibitor that specifically blocks the functions of Polo-Box domain. Oncotarget. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_27902479