Differential regulation of polo-like kinase 1, 2, 3, and 4 gene expression in mammalian cells and tissues.
The four mammalian polo-like kinase (Plk) family members are critical regulators of cell cycle progression, mitosis, cytokinesis, and the DNA damage response. Research conducted to date has primarily investigated the expression patterns, structural features, substrates, and subcellular distribution of these important serine-threonine kinases. Here, we review the published data describing the regulation of Plk1, 2, 3, or 4 gene expression either during mammalian cell cycle progression or in tissue samples. These studies have demonstrated that the Plk family genes are differentially expressed following growth factor stimulation of quiescent fibroblasts. Furthermore, although Plk1 and Plk2 mRNA and protein levels are coordinately regulated during cell cycle progression, this is not the case for Plk3. In addition, the Plk1, 2 and 4 proteins have relatively short intracellular half-lives, but Plk3 is very stable. The Plk family genes are also differentially regulated in stressed cells; for example, when DNA-damaging agents are added to cycling cells, Plk1 expression decreases, but Plk2 and Plk3 expression increases. Finally, Plk1, 2, 3, and 4 are expressed to varying degrees in different human tissue types and it has been reported that Plk1 expression is increased and Plk3 expression is decreased in tumor specimens. These results indicate that the differential regulation of Plk family member gene expression is one cellular strategy for controlling Plk activity in mammalian cells.
Winkles
Jeffrey A
JA
Department of Surgery, University of Maryland Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. jwinkles@som.umaryland.edu
Alberts
Gregory F
GF
D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; D000097868:Polo-like Kinases
D018797:Cell Cycle Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C486256:PLK3 protein, human; D000097868:Polo-like Kinases; C490219:PLK4 protein, human; C496126:PLK2 protein, human