On the Regulation and Function of Human Polo-like Kinase 1 (PLK1): Effects of Overexpression on Cell Cycle Progression

The human protein kinase Plk1, a member of the polo-like kinase family, is known to function at mitosis. Here we show that the relative specific activity of Plk1 increases in mitosis, that Plk1 is specifically phosphorylated during mitosis, and that phosphatase treatment reduces mitotic Plk1 activit...

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Veröffentlicht in:Biochemical and biophysical research communications 1997-10, Vol.239 (2), p.377-385
Hauptverfasser: Mundt, K.E., Golsteyn, R.M., Lane, H.A., Nigg, E.A.
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container_issue 2
container_start_page 377
container_title Biochemical and biophysical research communications
container_volume 239
creator Mundt, K.E.
Golsteyn, R.M.
Lane, H.A.
Nigg, E.A.
description The human protein kinase Plk1, a member of the polo-like kinase family, is known to function at mitosis. Here we show that the relative specific activity of Plk1 increases in mitosis, that Plk1 is specifically phosphorylated during mitosis, and that phosphatase treatment reduces mitotic Plk1 activity to interphase levels. To identify domains involved in the regulation of Plk1 activity, deletion mutants of Plk1 were constructed and their activities examined. Deletion of the extreme C-terminus of Plk1 substantially increased kinase activity, indicating that the C-terminus harbors an inhibitory domain. Finally, the consequences of over-production of wild-type and mutant Plk1 protein were analyzed, using transient transfection assays. Cells overexpressing Plk1 protein were able to enter mitosis and establish an apparently normal bipolar spindle. In contrast, progression through mitosis was transiently delayed, and cytokinesis appeared to be disturbed, as reflected by a significant increase in large cells with multiple, often fragmented nuclei. These results are relevant to recently proposed roles for Plks during both entry into and exit from mitosis.
doi_str_mv 10.1006/bbrc.1997.7378
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subjects Cell Cycle
Cell Cycle Proteins
Enzyme Activation - genetics
G2 Phase
HeLa Cells
Humans
Mitosis
Mutagenesis
Phosphorylation
Polo-Like Kinase 1
Protein Kinases - biosynthesis
Protein Kinases - genetics
Protein Kinases - metabolism
Protein Kinases - physiology
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins
Sequence Deletion
title On the Regulation and Function of Human Polo-like Kinase 1 (PLK1): Effects of Overexpression on Cell Cycle Progression
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