Polo-like Kinase 1 as an emerging drug target: structure, function and therapeutic implications

• Published in: Journal of drug targeting Vol. 29; no. 2; pp. 168 - 184
• Main Authors: Shakeel, Ilma, Basheer, Neha, Hasan, Gulam Mustafa, Afzal, Mohammad, Hassan, Md. Imtaiyaz
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 07.02.2021
• Subjects: Animals; anticancer therapy; apoptosis; Apoptosis - drug effects; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - metabolism; Cell Proliferation - drug effects; cell signalling; drug discovery; drug targeting; Humans; kinase inhibitors; Mitosis - drug effects; Molecular Targeted Therapy; Neoplasms - drug therapy; Neoplasms - enzymology; Polo-Like Kinase 1; Protein Kinase Inhibitors - pharmacology; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - metabolism; drug targeting; Polo-like Kinase 1; kinase inhibitors; drug discovery; cell signalling; anticancer therapy; apoptosis
• ISSN: 1061-186X; 1029-2330
• DOI: 10.1080/1061186X.2020.1818760

Polo-like kinase 1 (PLK1) is a conserved mitotic serine-threonine protein kinase, functions as a regulatory protein, and is involved in the progression of the mitotic cycle. It plays important roles in the regulation of cell division, maintenance of genome stability, in spindle assembly, mitosis, and DNA-damage response. PLK1 is consist of a N-terminal serine-threonine kinase domain, and a C-terminal Polo-box domain (regulatory site). The expression of PLK1 is controlled by transcription repressor in the G1 stage and transcription activators in the G2 stage of the cell cycle. Overexpression of PLK1 results in undermining of checkpoints causes excessive cellular division resulting in abnormal cell growth, leading to the development of cancer. Blocking the expression of PLK1 by an antibody, RNA interference, or kinase inhibitors, causes a subsequent reduction in the proliferation of tumour cells and induction of apoptosis in tumour cells without affecting the healthy cells, suggesting an attractive target for drug development. In this review, we discuss detailed information on expression, gene and protein structures, role in different diseases, and progress in the design and development of PLK1 inhibitors. We have performed an in-depth analysis of the PLK1 inhibitors and their therapeutic implications with special focus to the cancer therapeutics.