APC/CFzr/Cdh1-Dependent Regulation of Planar Cell Polarity Establishment via Nek2 Kinase Acting on Dishevelled

Weber, Ursula; Mlodzik, Marek

doi:10.1016/j.devcel.2016.12.006

Cited by 18 publications

(20 citation statements)

References 93 publications

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“…KEGG and GO enrichment analyses were conducted and revealed that NEK2 was mainly enriched in cell cycle and mitosis-related pathways. Many studies have suggested that NEK2 is a kinase implicated in regulating the S/G2 phase in cell cycle (Pfleger and Kirschner, 2000;Weber and Mlodzik, 2017). Notably, NEK2 is involved in the separation of centrosomes.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Exosome-Derived miR-486-5p Regulates Cell Cycle, Proliferation and Metastasis in Lung Adenocarcinoma via Targeting NEK2

et al. 2020

Front. Bioeng. Biotechnol.

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Objective: This study aimed to describe the mechanism of exosome-derived miR-486-5p underlying the cell cycle and progression in lung adenocarcinoma (LUAD). Methods: Bioinformatics methods were applied for identifying the differentially expressed genes (DEGs) in the GEO-LUAD dataset, predicting where the potential target miRNA was expressed and exploring the corresponding downstream target mRNA. qRT-PCR was conducted to detect the levels of the target genes in cancer cells. Thereafter, a series of in vitro experiments were performed for cell activities evaluation, including CCK-8, EdU, colony formation assay and transwell. Besides, Western blot was applied to determine the protein levels of the migration and invasion-related factors (NEK2, E-cadherin, N-cadherin, Vimentin, MMP-2, and MMP-9). Dual-luciferase reporter gene assay was employed for validating the targeted relationship between the target genes. Furthermore, nude mouse transplantation tumor experiment was conducted to further validate the role of the target miRNA in tumor development, and immunohistochemistry was used for Ki67 detection and TUNEL was applied for cell apoptosis assay. Results: miR-486-5p was observed to be enriched in serum exosomes, and seen to be significantly down-regulated in cancer tissues as well as in cancer serum exosomes. It was proven that exosomes could release miR-486-5p, thus regulating LUAD progression and affecting cell cycle. Moreover, NEK2 was identified as a target of miR-486-5p both in vivo and in vitro. Enrichment analysis revealed that NEK2 was mainly activated in cell cycle and mitosis-related pathways. Meanwhile, NEK2 was found to present significant difference in different TNM stages. Furthermore, rescue experiments indicated that the inhibitory effect of miR-486-5p overexpression on LUAD progression could be abrogated when miR-486-5p and NEK2 were simultaneously up-regulated. Conclusion: Exosome-derived miR-486-5p is responsible for cell cycle arrest as well as the inhibition of cell proliferation and metastasis in LUAD via targeting NEK2.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Exosome-Derived miR-486-5p Regulates Cell Cycle, Proliferation and Metastasis in Lung Adenocarcinoma via Targeting NEK2

et al. 2020

Front. Bioeng. Biotechnol.

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“…Moreover, APC/C Fzr regulates the transition from mitosis into endoreplication cycles in the Drosophila salivary gland, leading to the formation of polytene chromosomes (Zielke et al, 2008). Besides its well-known function during mitosis, the APC/C has been shown to also have essential cell-cycle-independent roles (for example, see Braun et al, 2018 preprint;Martins et al, 2017;Meghini et al, 2016;Neuert et al, 2017;Silies and Klämbt, 2010;van Roessel et al, 2004;Weber and Mlodzik, 2017).…”

Section: Introductionmentioning

confidence: 99%

APC/CFzr regulates cardiac and myoblast cell numbers, and plays a crucial role during myoblast fusion

Drechsler

Meyer

Wilmes

et al. 2018

Journal of Cell Science

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Somatic muscles are formed by the iterative fusion of myoblasts into muscle fibres. This process is driven by the recurrent recruitment of proteins to the cell membrane to induce F-actin nucleation at the fusion site. Although several proteins involved in myoblast fusion have been identified, knowledge about their subcellular regulation is rather elusive. We identified the anaphase-promoting complex (APC/C) adaptor Fizzy related (Fzr) as an essential regulator of heart and muscle development. We show that APC/C regulates the fusion of myoblasts as well as the mitotic exit of pericardial cells, cardioblasts and myoblasts. Surprisingly, overproliferation is not causative for the observed fusion defects. Instead, mutants exhibit smaller F-actin foci at the fusion site and display reduced membrane breakdown between adjacent myoblasts. We show that lack of APC/C causes accumulation and mislocalisation of Rols and Duf, two proteins involved in the fusion process. Duf seems to serve as direct substrate of the APC/C and its destruction depends on the presence of distinct degron sequences. These novel findings indicate that protein destruction and turnover constitute major events during myoblast fusion.

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“…In the fruit fly, different postmitotic roles have been described for the APC/C. It controls synaptic size via the downstream effector Liprin-alpha at the larval neuromuscular junction, acts during the establishment of planar cell polarity and functions in neurons of the embryonic peripheral nervous system (PNS) to control glial migration (Silies and Klämbt, 2010;van Roessel et al, 2004;Weber and Mlodzik, 2017). As mentioned above, Drosophila peripheral glial cells migrate along the axons of the motoneurons, which are decorated with a gradient of the Ig-domain cell-adhesion molecule Fasciclin 2 (Fas2).…”

Section: Introductionmentioning

confidence: 99%

Different modes of APC/C activation control growth and neuron-glia interaction in the developing Drosophila eye

et al. 2017

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The development of the nervous system requires tight control of cell division, fate specification and migration. The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that affects different steps of cell cycle progression, as well as having postmitotic functions in nervous system development. It can therefore link different developmental stages in one tissue. The two adaptor proteins, Fizzy/Cdc20 and Fizzy-related/Cdh1, confer APC/C substrate specificity. Here, we show that two distinct modes of APC/C function act during eye development. Fizzy/Cdc20 controls the early growth of the eye disc anlage and the concomitant entry of glial cells onto the disc. In contrast, acts during neuronal patterning and photoreceptor axon growth, and subsequently affects neuron-glia interaction. To further address the postmitotic role of Fzr/Cdh1 in controlling neuron-glia interaction, we identified a series of novel APC/C candidate substrates. Four of our candidate genes are required for -dependent neuron-glia interaction, including the dynein light chain Taken together, our data show how different modes of APC/C activation can couple early growth and neuron-glia interaction during eye disc development.

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APC/CFzr/Cdh1-Dependent Regulation of Planar Cell Polarity Establishment via Nek2 Kinase Acting on Dishevelled

Cited by 18 publications

References 93 publications

RETRACTED: Exosome-Derived miR-486-5p Regulates Cell Cycle, Proliferation and Metastasis in Lung Adenocarcinoma via Targeting NEK2

RETRACTED: Exosome-Derived miR-486-5p Regulates Cell Cycle, Proliferation and Metastasis in Lung Adenocarcinoma via Targeting NEK2

APC/CFzr regulates cardiac and myoblast cell numbers, and plays a crucial role during myoblast fusion

Different modes of APC/C activation control growth and neuron-glia interaction in the developing Drosophila eye

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