Specialize and Divide (Twice): Functions of Three Aurora Kinase Homologs in Mammalian Oocyte Meiotic Maturation

Nguyen, Alexandra L.; Schindler, Karen

doi:10.1016/j.tig.2017.03.005

Cited by 39 publications

(33 citation statements)

References 109 publications

(115 reference statements)

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“…In mitosis, the kinetochore-resident kinase Aurora-B plays a key role in promoting microtubule turnover at the kinetochore, thereby allowing for establishment of new attachments, a process dubbed 'error correction' [55]. Mammalian oocytes possess an additional Aurora-B homolog with at least partially overlapping functions, termed Aurora-C, though why two homologues are required has yet to be clarified [56,57]. Chemical inhibitors of Aurora-B/C or genetic disruption of Aurora-C in oocytes causes an accumulation of microtubule attachment errors, implying error correction normally plays a role in meiosis-I [36,56].…”

Section: Current Biologymentioning

confidence: 99%

Segregating Chromosomes in the Mammalian Oocyte

Mihajlović

FitzHarris

2018

Current Biology

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Chromosome segregation errors in human oocytes lead to aneuploid embryos that cause infertility and birth defects. Here we provide an overview of the chromosome-segregation process in the mammalian oocyte, highlighting mechanistic differences between oocytes and somatic cells that render oocytes so prone to segregation error. These differences include the extremely large size of the oocyte cytoplasm, the unique geometry of meiosis-I chromosomes, idiosyncratic function of the spindle assembly checkpoint, and dramatically altered oocyte cell-cycle control and spindle assembly, as compared to typical somatic cells. We summarise recent work suggesting that aging leads to a further deterioration in fidelity of chromosome segregation by impacting multiple components of the chromosome-segregation machinery. In addition, we compare and contrast recent results from mouse and human oocytes, which exhibit overlapping defects to differing extents. We conclude that the striking propensity of the oocyte to mis-segregate chromosomes reflects the unique challenges faced by the spindle in a highly unusual cellular environment.

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Section: Current Biologymentioning

confidence: 99%

Segregating Chromosomes in the Mammalian Oocyte

Mihajlović

FitzHarris

2018

Current Biology

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“…In humans, Aurora A and Aurora B have essential functions in mitotic cell division (Bolanos-Garcia 2005; Barr and Gergely 2007;Vader and Lens 2008;Krenn and Musacchio 2015). The third human family member, Aurora C, plays a role in meiotic cell division, as well as the first mitotic divisions of the mammalian zygote (Fernandez-Miranda et al 2011;Yang et al 2015;Nguyen and Schindler 2017). The Aurora kinases share ∼70% homology in their catalytic domains, although their localization patterns and substrates are distinct, resulting in unique roles during cell division (Carmena et al 2009;Nguyen and Schindler 2017).…”

Section: The Aurora Kinase Familymentioning

confidence: 99%

“…It is also noteworthy that although Aurora C is primarily expressed in germ line cells, it is also expressed in human tumor cells, and its overexpression in noncancerous cells can result in cell transformation (Ehara et al 2003;Dutertre et al 2005;Ulisse et al 2006;Khan et al 2011;Tsou et al 2011). Discussions of Aurora C kinase and its functions can be found in recent reviews (Yang et al 2015;Nguyen and Schindler 2017).…”

Section: Aurora C Kinasementioning

confidence: 99%

Aurora A Kinase Function at Kinetochores

DeLuca

2017

Cold Spring Harb Symp Quant Biol

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One of the most important regulatory aspects of chromosome segregation is the ability of kinetochores to precisely control their attachment strength to spindle microtubules. Central to this regulation is Aurora B, a mitotic kinase that phosphorylates kinetochore substrates to promote microtubule turnover. A critical target of Aurora B is the kinetochore protein Ndc80/Hec1, which is a component of the NDC80 complex, the primary force-transducing link between kinetochores and microtubules. Although Aurora B is regarded as the "master regulator" of kinetochore-microtubule attachment, it is becoming clear that this kinase is not solely responsible for phosphorylating Hec1 and other kinetochore substrates to facilitate microtubule turnover. In particular, there is growing evidence that Aurora A kinase, whose activities at spindle poles have been extensively described, has additional roles at kinetochores in regulating the kinetochore-microtubule interface.

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“…Aurora kinases (AURKs) are a family of conserved serine/threonine protein kinases, which are involved in several stages of mitosis (6); three of family members are AURKA, AURKB and AURKc. These members are expressed in mitotic and meiotic cells (7), and AURKA localizes to the duplicate centrosomes at the beginning of the S phase, shifts to the bipolar spindle microtubules during mitosis, and moves to perinuclear components of the daughter cell at the end of mitosis (8). AURKA is also important in tumorigenesis and tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA

Song

Liu

et al. 2018

Int J Mol Med

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Gastric adenocarcinoma remains a life‑threatening disease, emphasizing the importance of gaining an improved understanding of signaling pathways involved in this disease, which can lead to the development of novel therapeutic methods targeting common molecular pathways shared across different types of gastric adenocarcinoma. The present study revealed phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and aurora kinase A (AURKA) gene alterations, which were involved in changes in the phenotypes of gastric cancer cells, including increased proliferation by cell counting kit‑8 assay and invasion capacity by Transwell invasion assay, and predicted survival rates by KM Plotter database in gastric cancer. The present study investigated the association between PTEN and AURKA. Western blotting revealed that phosphorylated (p)-AURKA correlated with two target genes, PTEN and AURKA. The downregulation of PTEN by small interfering (si)RNA not only increased the expression of AURKA at the mRNA and protein levels by western blotting and by reverse transcription‑quantitative PCR, but also increased the expression of p‑AURKA by western blotting and immunofluorescence analysis. In addition, western blotting and reverse transcription‑quantitative PCR revealed that the downregulation of AURKA affected the expression level of PTEN. Furthermore, PTEN suppressed the malignant phenotypic changes of gastric adenocarcinoma cells by regulating the expression of AURKA inhibited by p‑AURKA, suggesting that p‑AURKA may be the key mediator of the PTEN‑associated activation of AURKA and may be key in maintaining the PTEN‑induced malignant state of gastric adenocarcinoma cells. This hypothesis was confirmed by western blotting, and changes were observed in the protein expression of p‑AURKA and AURKA under conditions in which cells were treated with either MLN8237 or si‑PTEN transfection only, or with si‑PTEN transfection and MLN8237. Knockdown of the expression of PTEN altered the expression of p‑AKT, p‑glycogen synthase kinase 3β and β‑catenin, which are genes that have been reported to be involved in the development of gastric adenocarcinoma. The present study confirmed that p‑AURKA is important in the development of gastric adenocarcinoma and revealed a novel functional link between PTEN, AURKA and p‑AURKA activation. The results also suggest a novel drug design strategy in targeting PTEN and AURKA for more specific gastric cancer cell death that spares normal cells.

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Specialize and Divide (Twice): Functions of Three Aurora Kinase Homologs in Mammalian Oocyte Meiotic Maturation

Cited by 39 publications

References 109 publications

Segregating Chromosomes in the Mammalian Oocyte

Segregating Chromosomes in the Mammalian Oocyte

Aurora A Kinase Function at Kinetochores

Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA

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