Putting a bit into the polo-box domain of polo-like kinase 1.
Polo-like kinase 1 (Plk1) plays key roles in regulating various mitotic processes that are critical for cellular proliferation. A growing body of evidence suggests that Plk1 overexpression is tightly associated with the development of human cancers. Interestingly, various types of cancer cells are shown to be addicted to a high level of Plk1, and the reversal of Plk1 addiction appears to be an effective strategy for selectively killing cancer cells, but not normal cells. Therefore, Plk1 is considered an attractive anticancer drug target. Over the years, a large number of inhibitors that target the catalytic activity of Plk1 have been developed. However, these inhibitors exhibit significant levels of cross-reactivity with related kinases, including Plk2 and Plk3. Consequently, as an alternative approach for developing anti-Plk1 therapeutics, substantial effort is under way to develop inhibitors that target the C-terminal protein-protein interaction domain of Plk1, called the polo-box domain (PBD). In this communication, I will discuss the pros and cons of targeting the PBD in comparison to those of targeting the ATP-binding site within the kinase domain.
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 3118, Bethesda, MD 20892 USA.
Jung-Eun
JE
Park
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 3118, Bethesda, MD 20892 USA.
Tae-Sung
TS
Kim
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 3118, Bethesda, MD 20892 USA.
Lingjun
L
Meng
Division of Magnetic Resonance, Korea Basic Science Institute, 804-1, Yangcheong Ri, Ochang, 363-883 Chungbuk Republic of Korea.
Jeong K
JK
Bang
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, 363-883 Republic of Korea.
Bo Y
BY
Kim
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 3118, Bethesda, MD 20892 USA.
Kyung S
KS
Lee
Cancer therapy; Inhibitor; Polo-box domain; Polo-like kinase 1