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Polo-like kinase

About: Polo-like kinase is a(n) research topic. Over the lifetime, 1697 publication(s) have been published within this topic receiving 149752 citation(s).
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Journal ArticleDOI
16 Dec 1993-Nature
TL;DR: It is found that over expression of p21 inhibits the activity of each member of the cyclin/CDK family, and this results indicate that p21 may be a universal inhibitor of cyclin kinases.
Abstract: Deregulation of cell proliferation is a hallmark of neoplastic transformation. Alteration in growth control pathways must translate into changes in the cell-cycle regulatory machinery, but the mechanism by which this occurs is largely unknown. Compared with normal human fibroblasts, cells transformed with a variety of viral oncoproteins show striking changes in the subunit composition of the cyclin-dependent kinases (CDKs). In normal cells, CDKs exist predominantly in multiple quaternary complexes, each containing a CDK, cyclin, proliferating cell nuclear antigen and the p21 protein. However, in many transformed cells, proliferating cell nuclear antigen and p21 are lost from these multiprotein enzymes. Here we have investigated the significance of this phenomenon by molecular cloning of p21 and in vitro reconstitution of the quaternary cell-cycle kinase complexes. We find that p21 inhibits the activity of each member of the cyclin/CDK family. Furthermore, overexpression of p21 inhibits the proliferation of mammalian cells. Our results indicate that p21 may be a universal inhibitor of cyclin kinases.

3,370 citations



Journal ArticleDOI
TL;DR: This work has shown that Cdk activity is governed by a complex network of regulatory subunits and phosphorylation events whose precise effects on Cdk conformation have been revealed by recent crystallographic studies.
Abstract: Cyclin-dependent kinases (Cdks) play a well-established role in the regulation of the eukaryotic cell division cycle and have also been implicated in the control of gene transcription and other processes. Cdk activity is governed by a complex network of regulatory subunits and phosphorylation events whose precise effects on Cdk conformation have been revealed by recent crystallographic studies. In the cell, these regulatory mechanisms generate an interlinked series of Cdk oscillators that trigger the events of cell division.

2,109 citations


Journal ArticleDOI
01 Jun 2003-Cell Proliferation
TL;DR: This review provides an overview of deregulation of the cell cycle in cancer by focusing on mechanisms, i.e. regulation of cyclin‐dependent kinases (CDK) by cyclins, CDK inhibitors and phosphorylating events.
Abstract: The cell cycle is controlled by numerous mechanisms ensuring correct cell division. This review will focus on these mechanisms, i.e. regulation of cyclin-dependent kinases (CDK) by cyclins, CDK inhibitors and phosphorylating events. The quality checkpoints activated after DNA damage are also discussed. The complexity of the regulation of the cell cycle is also reflected in the different alterations leading to aber- rant cell proliferation and development of cancer. Consequently, targeting the cell cycle in general and CDK in particular presents unique opportunities for drug discovery. This review provides an overview of deregulation of the cell cycle in cancer. Different families of known CDK inhibitors acting by ATP competition are also discussed. Cur- rently, at least three compounds with CDK inhibitory activity (flavopiridol, UCN-01, roscovitine) have entered clinical trials.

1,517 citations


Journal ArticleDOI
TL;DR: Analysis of non-proline site-containing phosphopeptides identified two unique motifs that suggest there are at least two undiscovered mitotic kinases, suggesting that many of the proteins identified may be CDK substrates.
Abstract: The eukaryotic cell division cycle is characterized by a sequence of orderly and highly regulated events resulting in the duplication and separation of all cellular material into two newly formed daughter cells. Protein phosphorylation by cyclin-dependent kinases (CDKs) drives this cycle. To gain further insight into how phosphorylation regulates the cell cycle, we sought to identify proteins whose phosphorylation is cell cycle regulated. Using stable isotope labeling along with a two-step strategy for phosphopeptide enrichment and high mass accuracy mass spectrometry, we examined protein phosphorylation in a human cell line arrested in the G1 and mitotic phases of the cell cycle. We report the identification of >14,000 different phosphorylation events, more than half of which, to our knowledge, have not been described in the literature, along with relative quantitative data for the majority of these sites. We observed >1,000 proteins with increased phosphorylation in mitosis including many known cell cycle regulators. The majority of sites on regulated phosphopeptides lie in [S/T]P motifs, the minimum required sequence for CDKs, suggesting that many of the proteins may be CDK substrates. Analysis of non-proline site-containing phosphopeptides identified two unique motifs that suggest there are at least two undiscovered mitotic kinases.

1,498 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20222
202119
202015
201923
201823
201742

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Topic's top 5 most impactful authors

Erich A. Nigg

32 papers, 8.8K citations

Klaus Strebhardt

16 papers, 2.3K citations

René H. Medema

10 papers, 3.5K citations

Viesturs Simanis

9 papers, 716 citations

Andrew M. Fry

7 papers, 901 citations