Mitotic kinases as regulators of cell division and its checkpoints

Nigg, Erich A.

doi:10.1038/35048096

Cited by 1,378 publications

(1,285 citation statements)

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“…Geminin, which prevents relicensing of replication origins after the initiation of DNA synthesis, is only present in cells progressing through S, G 2 and M phases, as are the mitotic engine kinases Plk1, Aurora A and Aurora B [74,107,108]. These three kinases control most mitotic events, including centrosome maturation and separation, chromosome orientation and segregation [8]. Notably, histone H3 is a substrate for the Aurora kinases and is phosphorylated at serine 10 only during the length of M phase [108,109].…”

Section: Geminin Mitotic Kinases and Phosphohistone H3 Can Be Used Tmentioning

confidence: 99%

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The cell cycle and cancer

Williams

Stoeber

2011

The Journal of Pathology

579

406

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Deregulation of the cell cycle underlies the aberrant cell proliferation that characterizes cancer and loss of cell cycle checkpoint control promotes genetic instability. During the past two decades, cancer genetics has shown that hyperactivating mutations in growth signalling networks, coupled to loss of function of tumour suppressor proteins, drives oncogenic proliferation. Gene expression profiling of these complex and redundant mitogenic pathways to identify prognostic and predictive signatures and their therapeutic targeting has, however, proved challenging. The cell cycle machinery, which acts as an integration point for information transduced through upstream signalling networks, represents an alternative target for diagnostic and therapeutic interventions. Analysis of the DNA replication initiation machinery and mitotic engine proteins in human tissues is now leading to the identification of novel biomarkers for cancer detection and prognostication, and is providing target validation for cell cycle-directed therapies.

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Section: Geminin Mitotic Kinases and Phosphohistone H3 Can Be Used Tmentioning

confidence: 99%

“…Cyclin D-CDK4, cyclin D-CDK6 and cyclin E-CDK2 drive G 1 progression through the restriction point, which commits the cell to complete the cycle [7]. S phase is initiated by cyclin A-CDK2, and cyclin B-CDK1 regulates progression through G 2 and entry into mitosis [8].…”

Section: Introductionmentioning

confidence: 99%

The cell cycle and cancer

Williams

Stoeber

2011

The Journal of Pathology

579

406

View full text Add to dashboard Cite

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“…Mitotic kinases, such as Cdk1, polo-like kinase 1 (Plk1), Aurora-A, and Aurora-B, are known to play a critical role in mitotic events including centrosome separation, chromosome condensation, nuclear envelope breakdown, and microtubule reorganization (Nigg et al, 1996;Nigg, 1998Nigg, , 2001Severson et al, 2000;Hirota et al, 2003). The serine/threonine protein kinase Plk1 contributes to normal mitotic phase progression, and localizes at mitotic spindles in metaphase and then at the midbody in cytokinesis (Nigg et al, 1996;Yuan et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of the cytokinesis regulator ECT2 at G2/M phase stimulates association of the mitotic kinase Plk1 and accumulation of GTP-bound RhoA

et al. 2005

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The epithelial cell transforming gene 2 (ECT2) protooncogene encodes a Rho exchange factor, and regulates cytokinesis. ECT2 is phosphorylated in G2/M phases, but its role in the biological function is not known. Here we show that two mitotic kinases, Cdk1 and polo-like kinase 1 (Plk1), phosphorylate ECT2 in vitro. We identified an in vitro Cdk1 phosphorylation site (T412) in ECT2, which comprises a consensus phosphospecific-binding module for the Plk1 polo-box domain (PBD). Endogenous ECT2 in mitotic cells strongly associated with Plk1 PBD, and this binding was inhibited by phosphatase treatment. A phosphorylation-deficient mutant form of ECT2, T412A, did not exhibit strong association with Plk1 PBD compared with wild-type (WT) ECT2. Moreover, ECT2 T412A, but not phosphomimic T412D, displayed a diminished accumulation of GTP-bound RhoA compared with WT ECT2, suggesting that phosphorylation of Thr-412 is critical for the catalytic activity of ECT2. Moreover, while overexpression of WT ECT2 or the T412D mutant caused cortical hyperactivity in U2OS cells during cell division, this activity was not observed in cells expressing ECT2 T412A. These results suggest that ECT2 is regulated by Cdk1 and Plk1 in concert.

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“…Besides the difference in the primary structure of these three kinases, their subcellular localization and functional regulation are distinctly different (Tab 1). Since this review is written mainly from the perspective of Aurora kinases in human, for the sake of clarity, we adapted the nomenclature proposed by Bischoff and Plowman [7] and substantiated by Nigg [1].…”

Section: Aurora/ipl1-related Kinases In Different Organismsmentioning

confidence: 99%

“…There are several protein kinase families that play distinct roles in different stages of mitosis [1]. The mitotic master kinase is cyclin B-dependent kinase (Cdk1), the founding member of the Cdk family of cell cycle regulators.…”

Section: Introductionmentioning

confidence: 99%

Function and regulation of Aurora/Ipl1p kinase family in cell division

Dou

Zhang

et al. 2003

Cell Res

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During mitosis, the parent cell distributes its genetic materials equally into two daughter cells through chromosome segregation, a complex movements orchestrated by mitotic kinases and its effector proteins. Faithful chromosome segregation and cytokinesis ensure that each daughter cell receives a full copy of genetic materials of parent cell. Defects in these processes can lead to aneuploidy or polyploidy. Aurora/Ipl1p family, a class of conserved serine/threonine kinases, plays key roles in chromosome segregation and cytokinesis. This article highlights the function and regulation of Aurora/Ipl1p family in mitosis and provides potential links between aberrant regulation of Aurora/Ipl1p kinases and pathogenesis of human cancer.

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Mitotic kinases as regulators of cell division and its checkpoints

Cited by 1,378 publications

References 114 publications

The cell cycle and cancer

The cell cycle and cancer

Phosphorylation of the cytokinesis regulator ECT2 at G2/M phase stimulates association of the mitotic kinase Plk1 and accumulation of GTP-bound RhoA

Function and regulation of Aurora/Ipl1p kinase family in cell division

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