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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.


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Posted ContentDOI
29 Feb 2016-bioRxiv
TL;DR: It is suggested that the same activity that triggers mitosis in an unperturbed cell cycle drives senescence in the presence of DNA damage, ensuring a robust response when most needed.
Abstract: In response to DNA damage a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity is retained after DNA damage until terminal cell cycle exit. The low level of Cdk activity not only allows cell cycle progression, but also forces cell cycle exit at a decision point in G2 phase. We find that Cdk activity stimulates p21 production, leading to nuclear sequestration of Cyclin B1, subsequent APC/CCdh1-dependent degradation of mitotic inducers and induction of senescence. We suggest that the same activity that triggers mitosis in an unperturbed cell cycle drives senescence in the presence of DNA damage, ensuring a robust response when most needed.

1 citations

Dissertation
27 Jul 2016
TL;DR: This work aimed to elucidate the regulation of mitosis in C. albicans, a poorly understood process, and focussed on characterizing the roles of a Polo-like kinase (Plk), Cdc5p, and discovered a novel, Candida-specific factor, CPI1, which was not essential for growth but required to maintain mitotic arrest and may interact with the splicesome.
Abstract: Candida albicans is a commensal fungus in humans, but can cause infections with high mortality rates. Cell proliferation and differentiation between yeast and hyphae are important for virulence and survival in the host. An understanding of their regulation may reveal new targets for therapeutic strategies. My work aimed to elucidate the regulation of mitosis in C. albicans, a poorly understood process, and focussed on characterizing the roles of a Polo-like kinase (Plk), Cdc5p. Plks are critical regulators of many aspects of mitosis in diverse organisms. Previous work demonstrated that depleting Cdc5p in C. albicans yeast resulted in a block in spindle elongation and mitosis, followed by formation of filaments and expression of hyphal-specific virulence genes, under yeast growth conditions. However, the mechanisms underlying Cdc5p function, mitotic progression, formation of novel filaments and expression of virulence genes, remained unclear. In order to address these questions, I first investigated a putative Cdc5p target, the Anaphase-Promoting Complex/Cyclosome (APC/C). In Chapter 2, I showed that APC/C co-activators Cdc20p and Cdh1p had some conservation in mitotic function, and may lie downstream of Cdc5p. However, additional novel features suggest variations in the mitotic circuitry. I next investigated the identity of the Cdc5p-depleted filaments, since this was controversial. We hypothesized that the cells were elongated yeast buds that failed to switch from polar to isometric growth, but adapted a hyphal fate over time due to maintenance of polarized growth. In Chapter 3, time course assays demonstrated that hyphal-diagnostic features emerged in Cdc5p-depleted filaments at only later growth stages, in agreement with our hypothesis. Our results expand on the strategies that C. albicans can utilize to modulate growth and virulence determinants. I further addressed the mechanisms of Cdc5p function during mitosis and morphogenesis in Chapter 4 by screening for interacting factors. I discovered a novel, Candida-specific factor, CPI1 (C. albicans Plk-interacting protein), which was not essential for growth but required to maintain mitotic arrest and may interact with the splicesome. Collectively, the work enhances our knowledge of mitotic regulation in C. albicans, and underscores variations in the regulatory circuitry that have important implications for controlling growth.

1 citations

Patent
19 Dec 2003
TL;DR: In this article, the nucleic acid sequences encoding Hemipteran polo-like kinases, and recombinant expressions and host cells comprising the same are disclosed, as well as the methods of producing the HemipTERAN-Polo-Like kinases and antibodies specific for the same.
Abstract: Novel nucleic acid sequences encoding Hemipteran polo-like kinases, and recombinant expressions and host cells comprising the same are disclosed. Isolated Hemipteran polo-like kinases, host cells expressing Hemipteran polo-like kinases, methods of producing the Hemipteran polo-like kinases and antibodies specific for Hemipteran polo-like kinases are also disclosed. Methods of identifying modulators and/or inhibitors of Hemipteran polo-like kinases are disclosed
Book ChapterDOI
01 Jan 1997
TL;DR: The cyclin kinase inhibitor WAF1 plays a central role in mediating the transition from a proliferative to a differentiated phenotype through its capacity to inhibit cyclin Dl activity and to prevent the Gi/S transition.
Abstract: This chapter discusses various aspects of cell cycle control. Progression around the cell cycle is governed by a family of cyclin-dependent kinases (CDKs) and their regulatory subunits the cyclins. As cells enter the cell cycle from G 0 -, D- and E-cyclins are synthesized sequentially and both are rate limiting for the S phase entry. The activities of the CDK family are in turn regulated by CDK inhibitors (CDIs). These include WAFl, the INK4 family, KIPl, and KIP2. WAF1 mediates p53 -dependent G 1 arrest by inhibiting cyclin D/CDK4, cyclin E/CDK2, and cyclin A/CDK2 through interaction with the cyclin component of the complexes. Independent effects of WAF1 on PCNA are the inhibition of its capacity to activate DNA polymerase 3 and the prevention of its interaction with GADD45 which is probably involved in stimulating DNA excision repair. The induction of WAF1 by p53 causes both cell cycle arrest and inhibition of DNA synthesis. The cyclin kinase inhibitor WAF1 plays a central role in mediating the transition from a proliferative to a differentiated phenotype through its capacity to inhibit cyclin Dl activity and to prevent the Gi/S transition. Mutant forms of CDK4 have been detected and CDK4 and CDK6 are over-expressed or amplified in some primary tumors and derived cell lines. The cyclin-dependent kinase activator CDC25B is over-expressed in nearly 30% of primary human breast cancers examined and this correlates with a less favorable prognosis.
DissertationDOI
01 Jan 2005
TL;DR: It is determined that the conserved phosphorylation sites of the NDR protein kinase family are required for Dbf2 kinase activity in vitro as well as for DBF2 function in vivo.
Abstract: Cyclin-dependent kinases (Cdk) direct cell cycle transitions by associating with various cyclins throughout the cell cycle. For cells to exit mitosis, mitotic Cdk activity must be turned off. In Saccharomyces cerevisiae, the mitotic exit network, or MEN, comprises of a group of proteins that form a signaling pathway required for mitotic exit. The MEN regulates the activity of Cdc14, the protein phosphatase critical for inactivating mitotic Cdk. Components of the MEN include the protein kinases Cdc15 and Dbf2, as well as the Dbf2-associated protein Mob1. We determined how these proteins are organized within the MEN by determining the molecular mechanism of Dbf2 activation. Dbf2 requires Mob1 association in order to be active and Cdc15 phosphorylates and thereby activates the Dbf2-Mob1 protein kinase complex. We also determined that the conserved phosphorylation sites of the NDR protein kinase family are required for Dbf2 kinase activity in vitro as well as for DBF2 function in vivo. It is unknown how Dbf2-Mob1 leads to Cdc14 release or how the protein kinase complex functions in cytokinesis. As a result, we sought to identify physiological substrates of Dbf2-Mob1 which would provide insight to Dbf2-Mob1 function in both of these significant cell cycle processes. There is no known physiological substrate for Dbf2-Mob1 we first identified RXXS as the motif that Dbf2-Mob1 preferentially phosphorylates. We then identified a number of in vitro substrates for Dbf2-Mob1, of which the majority contains the RXXS motif. The mechanism of Dbf2 activity has been shown to be conserved in a number of other NDR kinase family members, which have roles in morphogenesis and cell division, and have been implicated in tumorigenesis. Studies on Dbf2 will provide insight into cell cycle processes in budding yeast as well as in higher eukaryotes.

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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023111
202277
202119
202015
201923
201823