Polo-like kinase 1: target and regulator of transcriptional control.
Deregulated cell cycle control is a hallmark of cancer cells. Developmental or other mitogenic stimuli activate the proliferation of normal cells in response to the requirements of growing tissues. In contrast, cancer cells liberate from proliferative restrictions exerted by anti-proliferative signals arising from the stroma and by endogenous genetic programs that correlate to the terminal differentiation of cells. The study of cyclin-dependent kinases (Cdks) and polo-like kinases (Plks) as evolutionary conserved regulators of the cell cycle has contributed significantly to our current understanding of the mechanisms that underlie the proliferation of mammalian cells. Given the importance of Plk1 for mitotic progression the temporal expression of Plk1 is crucial and has to be tightly regulated. It is known that steady-state Plk1 mRNA and protein levels are coordinately regulated during cell cycle progression, being low during interphase but high in mitosis. This review will summarize the current knowledge on how cell cycle-dependent transcriptional regulation of the Plk1 gene is achieved. While binding sites for various transcriptional activators are dispersed throughout the entire Plk1 promoter region, the cell cycle-dependent regulation of the Plk1 gene expression seems to be regulated by G1-specific repression rather than by G2/M-specific activation of the Plk1 transcriptional unit. The tumor suppressor gene p53 was identified as a key player in the precise restriction of Plk1 gene expression to the G2/M phase. The activity of p53 is in turn controlled by Plk1 itself indicating the existence of an auto-regulatory mechanism involved in the cell cycle-dependent regulation of the Plk1 gene. Furthermore, transcription factors regulated by Plk1 will also be subject of discussion.
Martin
Bernd T
BT
Department of Gynecology and Obstetric, Medical School, J.W. Goethe-University, Frankfurt, Germany.
Strebhardt
Klaus
K
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1