Bimodal Interaction of Mammalian Polo-Like Kinase 1 and a Centrosomal Scaffold, Cep192, in the Regulation of Bipolar Spindle Formation

Meng, Lingjun; Park, Jung Eun; Kim, Tae Sung; Lee, Eun Hye; Park, Suk Youl; Zhou, Ming; Bang, Jeong Kyu; Lee, Kyung S.

doi:10.1128/mcb.00068-15

Cited by 44 publications

(78 citation statements)

References 32 publications

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“…Both kinases were localized with Cep192 during all oocyte maturation stages (Supplemental Fig. 2), consistent with previous results from somatic cells (18, 23).…”

Section: Resultssupporting

confidence: 91%

“…Chemical inhibition of PLK4 kinase activity reversibly depletes the centrioles in somatic cells (22), suggesting the importance of PLK4 in centriole duplication. In addition to PLK4, PLK1 and Aurora A kinase (AURKA) are involved in centrosome formation (18, 23). Both PLK1 and AURKA are recruited to Cep192, and it has been shown that both kinases reciprocally interact during their recruitment and activation (18, 23).…”

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confidence: 99%

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Distinct roles of Cep192 and Cep152 in acentriolar MTOCs and spindle formation during mouse oocyte maturation

Lee

Jung

et al. 2018

FASEB j.

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Mammalian oocytes lack a centriole that acts as a microtubule organization center (MTOC) in most somatic cells. During oocyte maturation, MTOCs undergo remodeling processes, including decondensation, fragmentation, and self-organization. However, the underlying mechanisms of MTOC remodeling in mouse oocytes are not well understood. We showed that two pericentriolar proteins, Cep192 and Cep152, play crucial roles during MTOC remodeling in mouse oocytes. Cep192 is present in MTOCs at all stages of oocyte maturation, and its depletion induces ablation of MTOCs, delay in spindle formation, and abnormal chromosomal alignment in spindles. In the case of Cep152, its localization on MTOCs is limited at the germinal vesicle stage and then disappears from the MTOCs after the germinal vesicle breakdown stage. Cep152 exclusion from MTOCs is involved in the fragmentation of MTOCs, and it is regulated by cyclin-dependent kinase 1 activity. Our results demonstrate the different roles of Cep192 and Cep152 in MTOC remodeling and a novel regulatory mechanism during meiotic spindle formation in mouse oocytes.-Lee, I.-W., Jo, Y.-J., Jung, S.-M., Wang, H.-Y., Kim, N.-H., Namgoong, S. Distinct roles of Cep192 and Cep152 in acentriolar MTOCs and spindle formation during mouse oocyte maturation.

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“…Both kinases were localized with Cep192 during all oocyte maturation stages (Supplemental Fig. 2), consistent with previous results from somatic cells (18, 23).…”

Section: Resultssupporting

confidence: 91%

mentioning

confidence: 99%

Distinct roles of Cep192 and Cep152 in acentriolar MTOCs and spindle formation during mouse oocyte maturation

Lee

Jung

et al. 2018

FASEB j.

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“…In addition to a role for CEP192 in controlling centrosome duplication, CEP192 promotes PCM expansion to allow for the formation of the mitotic spindle . Here, CEP192 recruits PLK1 and Aurora A to the centrosome in a cooperative fashion, resulting in their activation . The loss of CEP192 results in reduced γ‐tubulin recruitment to the centrosome and defective spindle formation .…”

Section: Introductionmentioning

confidence: 99%

FBXL 13 directs the proteolysis of CEP 192 to regulate centrosome homeostasis and cell migration

et al. 2018

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Aberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule nucleation. However, regulatory means of CEP192 have remained unknown. Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192. Among these, CEP192 is specifically targeted for proteasomal degradation by FBXL13. Accordingly, induced FBXL13 expression downregulates centrosomal γ-tubulin and disrupts centrosomal microtubule arrays. In addition, depletion of FBXL13 induces high levels of CEP192 and γ-tubulin at the centrosomes with the consequence of defects in cell motility. Together, we characterise FBXL13 as a novel regulator of microtubule nucleation activity and highlight a role in promoting cell motility with potential tumour-promoting implications.

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“…Perhaps any Polo binding sites in fly Spd-2 were simply not phosphorylated in the Y2H experiments. In support of this possibility, a single phosphorylated S-S/T(p) motif in SPD-2 and Cep192 is required for these proteins to efficiently recruit PLK1/Plk1 to centrosomes in worms (Decker et al, 2011) and frogs (Joukov et al, 2010), while two such S-S/T(p) motifs (one of which is conserved with the single motif identified in frogs) have been identified in human Cep192 (Meng et al, 2015).…”

Section: Introductionmentioning

confidence: 98%

“…In worms (Decker et al, 2011) and vertebrates (Joukov et al, 2014;Meng et al, 2015) SPD-2/Cep192 can help recruit PLK1/Plk1 to centrosomes and, in vertebrates, Cep192 can also activate Plk1, in part through recruiting and activating Aurora A, another mitotic protein kinase implicated in centrosome maturation. We suspected, therefore, that in flies Spd-2 might recruit Polo into the centrosomescaffold to phosphorylate Cnn and so help to generate a positive feedback loop that drives the expansion of the mitotic PCM.…”

Section: Introductionmentioning

confidence: 99%

A positive feedback loop drives centrosome maturation in flies

Alvarez‐Rodrigo

Conduit

Baumbach³

et al. 2018

Preprint

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Centrosomes are formed when mother centrioles recruit pericentriolar material (PCM) around themselves. The PCM expands dramatically as cells prepare to enter mitosis (a process termed centrosome maturation), but it is unclear how this expansion is achieved. In flies, Spd-2 and Cnn form an extensive scaffold around the mother centriole that recruits other components of the mitotic PCM, and the Polodependent phosphorylation of Cnn at the centrosome is crucial for scaffold assembly.Here we show that, like Cnn, Spd-2 is specifically phosphorylated at centrosomes. This phosphorylation appears to create multiple phosphorylated S-S/T(p) motifs that allow Spd-2 to recruit Polo to the expanding scaffold. If Spd-2 cannot recruit Polo to the expanding scaffold, the scaffold is initially assembled around the mother centriole, but it cannot expand outwards, and centrosome maturation fails. We conclude that Spd-2, Polo and Cnn cooperate to form a positive feedback loop that drives the dramatic expansion of the mitotic centrosome in flies.

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Bimodal Interaction of Mammalian Polo-Like Kinase 1 and a Centrosomal Scaffold, Cep192, in the Regulation of Bipolar Spindle Formation

Cited by 44 publications

References 32 publications

Distinct roles of Cep192 and Cep152 in acentriolar MTOCs and spindle formation during mouse oocyte maturation

Distinct roles of Cep192 and Cep152 in acentriolar MTOCs and spindle formation during mouse oocyte maturation

FBXL 13 directs the proteolysis of CEP 192 to regulate centrosome homeostasis and cell migration

A positive feedback loop drives centrosome maturation in flies

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