The mitosis-regulating and protein-protein interaction activities of Astrin are controlled by Aurora-A-induced phosphorylation

Chiu, Shao‐Chih; Chen, Jo Mei Maureen; Wei, Tong; Cheng, Tai Shan; Wang, Ya Hui Candice; Ku, Chia Feng; Lian, Chiao Hsuan; Liu, Chun Chih Jared; Kuo, Yi Chun; Yu, Chang Tze Ricky

doi:10.1152/ajpcell.00164.2014

Cited by 15 publications

(14 citation statements)

References 40 publications

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“…6b ), in agreement with a recent report 38 . Another interesting partner of CDC20B identified in a second unbiased interactome study 40 was SPAG5 (Astrin), which was reported to control timely activation of Separase during the cell cycle 41 , 42 . Using the same strategy as above, we could detect CDC20B and SPAG5 in the same complex (Fig.…”

Section: Resultsmentioning

confidence: 99%

CDC20B is required for deuterosome-mediated centriole production in multiciliated cells

et al. 2018

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Multiciliated cells (MCCs) harbor dozens to hundreds of motile cilia, which generate hydrodynamic forces important in animal physiology. In vertebrates, MCC differentiation involves massive centriole production by poorly characterized structures called deuterosomes. Here, single-cell RNA sequencing reveals that human deuterosome stage MCCs are characterized by the expression of many cell cycle-related genes. We further investigated the uncharacterized vertebrate-specific cell division cycle 20B (CDC20B) gene, which hosts microRNA-449abc. We show that CDC20B protein associates to deuterosomes and is required for centriole release and subsequent cilia production in mouse and Xenopus MCCs. CDC20B interacts with PLK1, a kinase known to coordinate centriole disengagement with the protease Separase in mitotic cells. Strikingly, over-expression of Separase rescues centriole disengagement and cilia production in CDC20B-deficient MCCs. This work reveals the shaping of deuterosome-mediated centriole production in vertebrate MCCs, by adaptation of canonical and recently evolved cell cycle-related molecules.

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Section: Resultsmentioning

confidence: 99%

CDC20B is required for deuterosome-mediated centriole production in multiciliated cells

et al. 2018

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“…In addition to what is known about Aurora B, it should be noted that Astrin also interacts with Aurora kinase A (AURKA), which is another member of the mitotic-regulated serine/threonine kinase family ( Bischoff and Plowman, 1999 ; Du et al, 2008 ; Chiu et al, 2014 ). Interestingly, the relationship between Astrin and Aurora A appears to have two distinct characteristics.…”

Section: The Dynamic Localization Of Astrin In Mitosismentioning

confidence: 99%

“…Second, Astrin is the phosphorylated substrate of Aurora A, and Aurora-A is essential for Astrin to regulate the activity of separase. Further, the Aurora A phosphorylation site of Astrin is important for the association of Astrin with additional interacting proteins including CLASP1, LC8, SKAP, and others ( Chiu et al, 2014 ). In short, the relationship between Astrin and Aurora A warrants further study.…”

Section: The Dynamic Localization Of Astrin In Mitosismentioning

confidence: 99%

Astrin: A Key Player in Mitosis and Cancer

Ying

Yang

et al. 2020

Front. Cell Dev. Biol.

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Astrin, which is a spindle-associated protein, was found to be closely related to mitotic spindle formation and maintenance. It interacts with other spindle-related proteins to play a key role in maintaining the attachment of the kinetochore-microtubule and integrity of centrosomes and promoting the centriole duplication. In addition, Astrin was quite recently found to be abnormally highly expressed in a variety of cancers. Astrin promotes the development of cancer by participating in various molecular pathways and is considered as a potential prognostic and survival predictor.

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“…Astrin is known to be phosphorylated at multiple sites (33,34), it is unclear whether Astrin phosphorylation by mitotic kinases regulates its KT targeting. This uncertainty prompted us to research other phosphorylation sites, the mitotic kinase(s) responsible for Astrin targeting to KTs, and the resulting KT structural ensemble.…”

Section: Astrin Is Phosphorylated In the N-terminal Region During Mitmentioning

confidence: 99%

“…Glycogen synthase kinase 3␤ (Gsk3␤) phosphorylates Astrin at Thr-111, Thr-937, Ser-974, and Thr-978 to regulate its spindle-forming ability but has no effect on localization (33). Aurora A regulates separase activity and the interaction of Astrin with Kinastrin/Skap and Clasp1␣ by phosphorylating Astrin at Ser-115 to promote mitotic progression (34).…”

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confidence: 99%

Phosphorylation of Astrin Regulates Its Kinetochore Function

Chung

Park

Lee

et al. 2016

Journal of Biological Chemistry

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The error-free segregation of chromosomes, which requires the precisely timed search and capture of chromosomes by spindles during early mitotic and meiotic cell division, is responsible for genomic stability and is achieved by the spindle assembly checkpoint in the metaphase-anaphase transition. Mitotic kinases orchestrate M phase events, such as the reorganization of cell architecture and kinetochore (KT) composition with the exquisite phosphorylation of mitotic regulators, to ensure timely and temporal progression. However, the molecular mechanisms underlying the changes of KT composition for stable spindle attachment during mitosis are poorly understood. Here, we show that the sequential action of the kinase Cdk1 and the phosphatase Cdc14A control spindle attachment to KTs. During prophase, the mitotic spindle protein Spag5/Astrin is transported into centrosomes by Kinastrin and phosphorylated at Ser-135 and Ser-249 by Cdk1, which, in prometaphase, is loaded onto the spindle and targeted to KTs. We also demonstrate that Cdc14A dephosphorylates Astrin, and therefore the overexpression of Cdc14A sequesters Astrin in the centrosome and results in aberrant chromosome alignment. Mechanistically, Plk1 acts as an upstream kinase for Astrin phosphorylation by Cdk1 and targeting phospho-Astrin to KTs, leading to the recruitment of outer KT components, such as Cenp-E, and the stable attachment of spindles to KTs. These comprehensive findings reveal a regulatory circuit for protein targeting to KTs that controls the KT composition change of stable spindle attachment and chromosome integrity.The maintenance of genome integrity during mitosis is crucial for cell survival and organismal development. To generate two daughter cells with identical genetic information, each sister chromatid must be captured by spindle microtubules (MTs), 4 aligned at the mitotic equator, and segregated toward the spindle poles. Cells build a proteinaceous structure, known as the KT, at the centromere and form a bipolar spindle with an amphitelic spindle attachment to achieve accurate chromosome segregation (1). The KT is made up of protein complexes that control its localization on the chromosome, assembly, attachment to spindle MTs, and chromosome movements, such as congression and segregation (2). KTs lacking essential proteins for KT-MT attachment, such as Knl1, Mis12, and Ndc80 protein subcomplexes, are unable to attach to spindle MTs (3), which in turn results in chromosome loss and concurrent cell death (4).Entry into mitosis is controlled by the concerted action of several mitotic kinases, such as Cyclin-dependent kinase 1 (Cdk1), Polo-like kinase 1 (Plk1), and Aurora A, whose activities are regulated indirectly in a positive feedback loop (5). Plk1 activates Cdk1 by phosphorylating and activating Cdc25, which then removes inhibitory phosphorylation at the Thr-14 and Tyr-15 sites of Cdk1. Aurora A phosphorylates Thr-210 in the active loop of Plk1 with the aid of Bora (6). Cdk1 also activates Plk1 via Bora phosphorylation to promote mit...

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The mitosis-regulating and protein-protein interaction activities of Astrin are controlled by Aurora-A-induced phosphorylation

Abstract: CT. The mitosis-regulating and protein-protein interaction activities of Astrin are controlled by Aurora-A-induced phosphorylation.

Cited by 15 publications

References 40 publications

CDC20B is required for deuterosome-mediated centriole production in multiciliated cells

CDC20B is required for deuterosome-mediated centriole production in multiciliated cells

Astrin: A Key Player in Mitosis and Cancer

Phosphorylation of Astrin Regulates Its Kinetochore Function

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