Aurora-PLK1 cascades as key signaling modules in the regulation of mitosis

Vladimir Joukov, Arcangela De Nicolo

Research output: Contribution to journalReview article

Abstract

Mitosis is controlled by reversible protein phosphorylation involving specific kinases and phosphatases. A handful of major mitotic protein kinases, such as the cyclin B-CDK1 complex, the Aurora kinases, and Polo-like kinase 1 (PLK1), cooperatively regulate distinct mitotic processes. Research has identified proteins and mechanisms that integrate these kinases into signaling cascades that guide essential mitotic events. These findings have important implications for our understanding of the mechanisms of mitotic regulation and may advance the development of novel antimitotic drugs. We review collected evidence that in vertebrates, the Aurora kinases serve as catalytic subunits of distinct complexes formed with the four scaffold proteins Bora, CEP192, INCENP, and TPX2, which we deem "core" Aurora cofactors. These complexes and the Aurora-PLK1 cascades organized by Bora, CEP192, and INCENP control crucial aspects of mitosis and all pathways of spindle assembly. We compare the mechanisms of Aurora activation in relation to the different spindle assembly pathways and draw a functional analogy between the CEP192 complex and the chromosomal passenger complex that may reflect the coevolution of centrosomes, kinetochores, and the actomyosin cleavage apparatus. We also analyze the roles and mechanisms of Aurora-PLK1 signaling in the cell and centrosome cycles and in the DNA damage response.

Original languageEnglish
Pages (from-to)1-25
Number of pages25
JournalScience Signaling
Volume11
Issue number543
DOIs
Publication statusPublished - Aug 14 2018

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Aurora Kinases
Mitosis
Centrosome
Phosphotransferases
Cyclin B
Antimitotic Agents
Kinetochores
Actomyosin
Phosphorylation
Proteins
Phosphoric Monoester Hydrolases
Scaffolds
Protein Kinases
DNA Damage
Vertebrates
Catalytic Domain
Cell Cycle
Chemical activation
DNA
Research

Cite this

Aurora-PLK1 cascades as key signaling modules in the regulation of mitosis. / Joukov, Vladimir; De Nicolo, Arcangela.

In: Science Signaling, Vol. 11, No. 543, 14.08.2018, p. 1-25.

Research output: Contribution to journalReview article

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AU - De Nicolo, Arcangela

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