The role of Plk3 in oncogenesis.
The polo-like kinases (Plks) encompass a family of five serine/threonine protein kinases that play essential roles in many cellular processes involved in the control of the cell cycle, including entry into mitosis, DNA replication and the response to different types of stress. Plk1, which has been validated as a cancer target, came into the focus of many pharmaceutical companies for the development of small-molecule inhibitors as anticancer agents. Recently, FDA (Food and Drug Administration) has granted a breakthrough therapy designation to the Plk inhibitor BI 6727 (volasertib), which provided a survival benefit for patients suffering from acute myeloid leukemia. However, the various ATP-competitive inhibitors of Plk1 that are currently in clinical development also inhibit the activities of Plk2 and Plk3, which are considered as tumor suppressors. Plk3 contributes to the control and progression of the cell cycle while acting as a mediator of apoptosis and various types of cellular stress. The aberrant expression of Plk3 was found in different types of tumors. Recent progress has improved our understanding of Plk3 in regulating stress signaling and tumorigenesis. When using ATP-competitive Plk1 inhibitors, the biological roles of Plk1-related family members like Plk3 in cancer cells need to be considered carefully to improve treatment strategies against cancer.
Department of Obstetrics and Gynecology, School of Medicine, J.W. Goethe University, Frankfurt, Germany.
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Helmke
Department of Obstetrics and Gynecology, School of Medicine, J.W. Goethe University, Frankfurt, Germany.
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Becker
Department of Obstetrics and Gynecology, School of Medicine, J.W. Goethe University, Frankfurt, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.
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Strebhardt
D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D063646:Carcinogenesis; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011621:Pteridines / Q000494:pharmacology; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; D000097868:Polo-like Kinases
D000255:Adenosine Triphosphate; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C541363:BI 6727; C486256:PLK3 protein, human; D000097868:Polo-like Kinases