Furry Protein Promotes Aurora A-mediated Polo-like Kinase 1 Activation

Ikeda, Masanori; Chiba, Shuhei; Ohashi, Kazumasa; Mizuno, Kensaku

doi:10.1074/jbc.m112.378968

Cited by 31 publications

(42 citation statements)

References 31 publications

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“…On the other hand, the DSR (named region 24, spans 28.58 to 29.84 Mb) with the highest number of top 0.1% SNPs was located on chromosome 10 (Table 1 and Figure 3). Furry homolog (Drosophila) ( FRY ), which included four of the top 0.1% SNPs of this region, is an evolutionarily conserved protein implicated in cell division and morphology [16]. Additionally, selection signals were detected for genes associated with economically important traits, i.e., MITF and GHR .…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Genetic Diversity and Differentially Selected Regions among Suffolk, Rambouillet, Columbia, Polypay, and Targhee Sheep

Zhang

Mousel²,

et al. 2013

PLoS ONE

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Sheep are among the major economically important livestock species worldwide because the animals produce milk, wool, skin, and meat. In the present study, the Illumina OvineSNP50 BeadChip was used to investigate genetic diversity and genome selection among Suffolk, Rambouillet, Columbia, Polypay, and Targhee sheep breeds from the United States. After quality-control filtering of SNPs (single nucleotide polymorphisms), we used 48,026 SNPs, including 46,850 SNPs on autosomes that were in Hardy-Weinberg equilibrium and 1,176 SNPs on chromosome × for analysis. Phylogenetic analysis based on all 46,850 SNPs clearly separated Suffolk from Rambouillet, Columbia, Polypay, and Targhee, which was not surprising as Rambouillet contributed to the synthesis of the later three breeds. Based on pair-wise estimates of F ST, significant genetic differentiation appeared between Suffolk and Rambouillet (F ST = 0.1621), while Rambouillet and Targhee had the closest relationship (F ST = 0.0681). A scan of the genome revealed 45 and 41 differentially selected regions (DSRs) between Suffolk and Rambouillet and among Rambouillet-related breed populations, respectively. Our data indicated that regions 13 and 24 between Suffolk and Rambouillet might be good candidates for evaluating breed differences. Furthermore, ovine genome v3.1 assembly was used as reference to link functionally known homologous genes to economically important traits covered by these differentially selected regions. In brief, our present study provides a comprehensive genome-wide view on within- and between-breed genetic differentiation, biodiversity, and evolution among Suffolk, Rambouillet, Columbia, Polypay, and Targhee sheep breeds. These results may provide new guidance for the synthesis of new breeds with different breeding objectives.

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Section: Resultsmentioning

confidence: 99%

Genome-Wide Genetic Diversity and Differentially Selected Regions among Suffolk, Rambouillet, Columbia, Polypay, and Targhee Sheep

Zhang

Mousel²,

et al. 2013

PLoS ONE

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“…In addition, other proteins such as Fry and CEP192 have been implicated in Aurora A-mediated Plk1 activation and could have an additional role in this process. 37, 38 …”

Section: Discussionmentioning

confidence: 99%

Inhibition of Polo-like kinase 1 during the DNA damage response is mediated through loss of Aurora A recruitment by Bora

et al. 2016

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When cells in G2 phase are challenged with DNA damage, several key mitotic regulators such as Cdk1/Cyclin B, Aurora A and Plk1 are inhibited to prevent entry into mitosis. Here we have studied how inhibition of Plk1 is established after DNA damage. Using a Förster resonance energy transfer (FRET)-based biosensor for Plk1 activity, we show that inhibition of Plk1 after DNA damage occurs with relatively slow kinetics and is entirely dependent on loss of Plk1-T210 phosphorylation. As T210 is phosphorylated by the kinase Aurora A in conjunction with its co-factor Bora, we investigated how they are affected by DNA damage. Interestingly, we find that the interaction between Bora and Plk1 remains intact during the early phases of the DNA damage response (DDR), whereas Plk1 activity is already inhibited at this stage. Expression of an Aurora A mutant that is refractory to inhibition by the DDR failed to prevent inhibition of Plk1 and loss of T210 phosphorylation, suggesting that inhibition of Plk1 may be established by perturbing recruitment of Aurora A by Bora. Indeed, expression of a fusion in which Aurora A was directly coupled to Bora prevented DNA damage-induced inhibition of Plk1 activity, as well as inhibition of T210 phosphorylation. Taken together, these data demonstrate that DNA damage affects the function of Aurora A at multiple levels: both by direct inhibition of Aurora A activity, as well as by perturbing the interaction with its co-activator Bora. We propose that the DDR targets recruitment of Aurora A to the Plk1/Bora complex to prevent activation of Plk1 during DNA damage in G2.

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“…In addition to the kinase cascades organized by Bora and CEP192, other AurA-PLK1 cascades may exist to allow fine-tuning of the spatiotemporal activity or more specialized functions of both kinases. In this regard, two proteins, Furry and Gravin [also called A-kinase anchoring protein 12 (AKAP12)], also promote PLK1 activation by AurA (139,140). Furry localizes to centrosomes and spindle poles and is required for spindle pole integrity but not for centrosome maturation and separation (139).…”

Section: Aura-plk1 Cascadesmentioning

confidence: 99%

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

Joukov¹,

2018

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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.

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Furry Protein Promotes Aurora A-mediated Polo-like Kinase 1 Activation

Cited by 31 publications

References 31 publications

Genome-Wide Genetic Diversity and Differentially Selected Regions among Suffolk, Rambouillet, Columbia, Polypay, and Targhee Sheep

Genome-Wide Genetic Diversity and Differentially Selected Regions among Suffolk, Rambouillet, Columbia, Polypay, and Targhee Sheep

Inhibition of Polo-like kinase 1 during the DNA damage response is mediated through loss of Aurora A recruitment by Bora

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

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