Polo-like kinase

About: Polo-like kinase is a research topic. Over the lifetime, 1697 publications have been published within this topic receiving 149752 citations.

Cyclins and cell cycle checkpoints

Abstract: The eucaryotic cell cycle is regulated by the periodic synthesis and destruction of cyclins that associate with and activate cyclin-dependent kinases. Cyclin-dependent kinase inhibitors, such as p21 and p16, also play important roles in cell cycle control by coordinating internal and external signals and impeding proliferation at several key checkpoints. Understanding how these proteins interact to regulate the cell cycle has become increasingly important to researchers and clinicians with the discovery that many of the genes that encode cell cycle regulatory activities are targets for alterations that underlie the development of cancer. Several therapeutic agents, such as DNA-damaging drugs, microtubule inhibitors, antimetabolites, and topoisomerase inhibitors, take advantage of this disruption in normal cell cycle regulation to target checkpoint controls and ultimately induce growth arrest or apoptosis of neoplastic cells. Other therapeutic drugs being developed, such as UCN-01, specifically inhibit cell cycle regulatory proteins.

Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes

Abstract: Mammalian polo-like kinase 1 (Plk1) is structurally related to the polo gene product of Drosophila melanogaster, Cdc5p of Saccharomyces cerevisiae, and plo1+ of Schizosaccharomyces pombe, a newly emerging family of serine-threonine kinases implicated in cell cycle regulation. Based on data obtained for its putative homologues in invertebrates and yeasts, human Plk1 is suspected to regulate some fundamental aspect(s) of mitosis, but no direct experimental evidence in support of this hypothesis has previously been reported. In this study, we have used a cell duplication, microinjection assay to investigate the in vivo function of Plk1 in both immortalized (HeLa) and nonimmortalized (Hs68) human cells. Injection of anti-Plk1 antibodies (Plk1+) at various stages of the cell cycle had no effect on the kinetics of DNA replication but severely impaired the ability of cells to divide. Analysis of Plk1(+)-injected, mitotically arrested HeLa cells by fluorescence microscopy revealed abnormal distributions of condensed chromatin and monoastral microtubule arrays that were nucleated from duplicated but unseparated centrosomes. Most strikingly, centrosomes in Plk1(+)-injected cells were drastically reduced in size, and the accumulation of both gamma-tubulin and MPM-2 immunoreactivity was impaired. These data indicate that Plk1 activity is necessary for the functional maturation of centrosomes in late G2/early prophase and, consequently, for the establishment of a bipolar spindle. Additional roles for Plk1 at later stages of mitosis are not excluded, although injection of Plk1+ after the completion of spindle formation did not interfere with cytokinesis. Injection of Plk1+ into nonimmortalized Hs68 cells produced qualitatively similar phenotypes, but the vast majority of the injected Hs68 cells arrested as single, mononucleated cells in G2. This latter observation hints at the existence, in nonimmortalized cells, of a centrosome-maturation checkpoint sensitive to the impairment of Plk1 function.

The Cell Cycle: Principles of Control

Abstract: 1 The Cell Cycle 2 Model Organisms in Cell-Cycle Analysis 3 The Cell-Cycle Control System 4 Chromosome Duplication 5 Early Mitosis: Preparing for Chromosome Segregation 6 Assembly of the Mitotic Spindle 7 The Completion of Mitosis 8 Cytokinesis 9 Meiosis 10 Control of Cell Proliferation and Growth 11 Cell-Cycle Respomses to DNA Damage 12 The Cell Cycle in Cancer

Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast.

Abstract: The control regulating commitment to the cell division cycle of eukaryotes seems to occur before the initiation of DNA replication1–4. In the budding yeast Saccharomyces cerevisiae, this control is called start and is the earliest gene-controlled event of the cell cycle3–5. A haploid cell which has completed start is committed to cell division and unable to undergo alternative developmental fates such as conjugation. Here, we describe an analogous start control in the fission yeast Schizosaccharomyces pombe. We have tested the ability of cdc mutants blocked at various stages of the cell cycle to undergo conjugation. Only mutants of cdc 2 and cdc 10 which block during the G1 period are able to conjugate. Other mutants which block during G1, S phase, G2 or mitosis are committed to cell division and cannot conjugate. The commitment control start is located in G1, and its completion requires the gene functions of cdc 2 and 10. Completion of start occurs at the beginning of the cell cycle in rapidly growing cells, but is delayed to later in the cell cycle at slow growth rates. The cdc 2 gene function also participates in another major cell cycle control which determines the timing of mitosis6–8. Therefore cdc 2 is a cell cycle control gene which acts at two separate points in the cell cycle: it is required in G1 for commitment to cell division and in G2 for the control of mitosis.