• 대한방사성의약품학회지
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• 제6권2호
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• pp.139-145
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• 2020

Polo-like kinase 1 (Plk1) is a key protein in mitosis and has been validated as a target for tumor therapy. It is well known to highly overexpress in many kinds of tumor, which has been implicated as a potential biomarker for tumor treatment and diagnosis. Plk1 consists of two domains, the N-terminus kinase domain and the C-terminus polo-box domain (PBD). The inhibitors have been developed for PBD of Plk1, which were shown a high level of affinity and selectivity for Plk1 that led to mitotic arrest and apoptotic cell death. This review discusses the inhibitors for PBD of Plk1 that are suitable for in vivo tumor treatment. They can be further extended for developing in vivo imaging probes for early diagnosis of tumor.

• 대한방사성의약품학회지
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• 제5권2호
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• pp.152-157
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• 2019

Polo-like kinase 1 (Plk1) is crucial regulator of cell cycle progression during mitosis. It is known to highly overexpress in many different tumor types, and has been implicated as a potential antimitotic cancer target. The phosphopeptide, Pro-Leu-His-Ser-p-Thr (PLHSpT), was shown a high level of affinity and specificity for the polo-box domain (PBD) of Plk1. However, the peptide has the limitation of cell permeability. We designed the derivatives to enhance the limitation of PLHSpT using drug delivery system. In addition, we synthesized and evaluated its radiotracer for tumor diagnosis. This review discusses the derivative and radiotracer that are suitable for tumor treatment and diagnosis for PBD of Plk1.

• BMB Reports
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• 제39권6호
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• pp.709-716
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• 2006

Mammalian polo-like kinase 1 (Plk1) acts at various stages in early and late mitosis. Plk1 localizes at the centrosome and maintains this position through mitosis. Thereafter Plk1 moves to the kinetochore and midbody region, important sites during chromosome separation and cytokinesis. The catalytic domain of Plk1 is in the N-terminus region, whereas the non-catalytic region in the C-terminus of Plk1 has a conserved motif, named the Polobox. This motif is critical for Plk localization. EGFP proteins fused with the N-terminus and C-terminus of Plk1 localize in the nucleus and centrosomes, respectively. The core sequences of the polo-box (50 amino acids) also localize in Plk1 target organelles. To screen for domain-specific target proteins of Plk1, we constructed an N-terminal domain and a tandem repeat polo-box motif, and used them as templates in a yeast two-hybrid screen. The HeLa cell cDNA library indicated several proteins including the centrosome/kinetochore components or regulators, to be characterized as positive clones. Through in vitro protein binding analyses, we confirmed an interaction between these proteins and Plk1. The data reported from this study indicate that the N- and C- termini of Plk1 may function through recruitment and/or activation of domain-specific target proteins in dividing cells. Additionally, tandem repeats of the conserved core motif of the polo-box are sufficient for targeting and may be useful as a centrosome/kinetochore-specific targeting peptide.

• Molecules and Cells
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• 제37권4호
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• pp.286-294
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• 2014

Mammalian polo-like kinase 1 (Plk1) has been studied intensively as a key regulator of various cell cycle events that are critical for proper M-phase progression. The polobox domain (PBD) present in Plk1's C-terminal noncatalytic region has been shown to play a central role in targeting the N-terminal kinase domain of Plk1 to specific subcellular locations. Subsequent studies reveal that PBD binds to a phosphorylated motif generated by one of the two mechanisms - self-priming by Plk1 itself or non-self-priming by a Pro-directed kinase, such as Cdc2. Here, we comparatively review the differences in the biochemical steps of these mechanisms and discuss their physiological significance. Considering the diverse functions of Plk1 during the cell cycle, a better understanding of how the catalytic activity of Plk1 functions in concert with its cisacting PBD and how this coordinated process is intricately regulated to promote Plk1 functions will be important for providing new insights into different mechanisms underlying various Plk1-mediated biological events that occur at the multiple stages of the cell cycle.