Cep55 promotes cytokinesis of neural progenitors but is dispensable for most mammalian cell divisions

Tedeschi, Antonio; Almagro, Jorge; Renshaw, Matthew J.; Messal, Hendrik A.; Behrens, Axel; Petronczki, Mark

doi:10.1038/s41467-020-15359-w

Cited by 42 publications

(56 citation statements)

References 71 publications

(132 reference statements)

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“…During the writing of this manuscript, another research group published the phenotype of a Cep55 knockout mouse (Tedeschi et al, 2020). They similarly found Cep55 -/-mice have microcephaly disproportionate to body size reduction, an accumulation of binucleate NSCs, and apoptosis specific to neural tissues.…”

Section: Discussionmentioning

confidence: 97%

Loss of Coiled-Coil Protein Cep55 Impairs Neural Stem Cell Abscission and Results in p53-Dependent Apoptosis in Developing Cortex

et al. 2021

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To produce a brain of normal size and structure, embryonic neural stem cell (NSCs) must tightly regulate their cell divisions. Cerebral cortex NSCs undergo a polarized form of cytokinesis whose regulation is poorly understood. Cytokinetic abscission severs the daughter cells and is mediated by the midbody at the apical membrane. Here we elucidate the role of the coiled-coil midbody protein Cep55 in NSC abscission and brain development. A knockout of Cep55 in mice causes microcephaly with reduced NSCs and neurons, but relatively normal body size. Fixed and live analyses show NSCs lacking Cep55 have decreased but not eliminated ESCRT recruitment, and have abnormal abscission and higher rates of failure. P53-mediated apoptosis is greatly increased in the brain, but not other tissues, and p53 knockout partly rescues brain size. Thus, loss of Cep55 causes abscission defects and failures in multiple cell types, but the secondary p53 response and apoptosis is brain-specific.

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Section: Discussionmentioning

confidence: 97%

Loss of Coiled-Coil Protein Cep55 Impairs Neural Stem Cell Abscission and Results in p53-Dependent Apoptosis in Developing Cortex

et al. 2021

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“…However, newly reported mouse knockout models reveal a more complex picture in vivo. In these mouse models, ALIX and CEP55 were found to be required for normal brain and kidney development and cell division, whereas other organs appear largely unaffected (Campos et al, 2016; Tedeschi et al, 2020). Moreover, humans without functional ALIX display microcephaly and kidney defects but are otherwise healthy and can live into their 20s (Khan et al, 2020).…”

Section: Discussionmentioning

confidence: 97%

Abscission Checkpoint Bodies Reveal a New Facet of Abscission Checkpoint Control

Williams

Mackay

Whitney

et al. 2020

Preprint

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The abscission checkpoint regulates the ESCRT membrane fission machinery and thereby delays cytokinetic abscission to protect genomic integrity in response to residual mitotic errors. The checkpoint is maintained by Aurora B kinase, which phosphorylates multiple targets, including CHMP4C, a regulatory ESCRT-III subunit necessary for this checkpoint. We now report the discovery that cytoplasmic abscission checkpoint bodies (ACBs) containing phospho-Aurora B and tri-phospho-CHMP4C develop in telophase under an active checkpoint. ACBs are derived from Mitotic Interchromatin Granules (MIGs), transient mitotic structures whose components are housed in splicing-related nuclear speckles during interphase. ACB formation requires CHMP4C, and the ESCRT factor ALIX also contributes. ACB formation is conserved across cell types and under multiple circumstances that activate the checkpoint. Finally, ACBs retain a population of ALIX, and their presence correlates with delayed recruitment of ALIX to the midbody where it would normally promote abscission. Thus, a cytoplasmic mechanism helps regulate midbody machinery to delay abscission.

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“…Centrosomal protein 55 (CEP55) is dispensable for mouse embryonic development and adult tissue homeostasis [29]. CEP55 mediates the physical separation of daughter cells and completes cell division through binding GPPX3Y motifs of ALIX and TSG101 to block similar GPPX3Y motifs of ALIX and TSG10 from interacting and localizing to the midbody [30].…”

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Biomarkers Associated with Ovarian Cancer Progression and Prognosis by Integrated Microarray Analysis

Chen

Jiachun

Feng

et al. 2021

Preprint

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Ovarian cancer (OC) is one of the most common gynecological malignancies, with high mortality and few prognostic biomarkers. This study aimed to identify differentially expressed genes (DEGs) relevant to the prognosis of ovarian cancer. First, we performed differential analysis on GSE38666, GSE14407, GSE27651 and GSE18520 expression profile datasets from the Gene Expression Omnibus (GEO) database and obtained 638 DEGs using a Venn diagram tool. Second, we constructed a protein–protein interaction (PPI) network with the STRING database and used the Molecular Complex Detection (MCODE) plugin in Cytoscape software to perform gene cluster analyses for 269 upregulated and 367 downregulated DEGs, respectively. Based on the results of gene cluster analyses, we selected two gene clusters of upregulated DEGs with network scores of > 10 and two gene clusters of downregulated DEGs with scores of > 5 for further functional analysis with the clusterProfiler package. In addition, we analyzed the effect of genes from those clusters on the overall survival (OS) and progression-free survival (PFS) of OC patients based on Kaplan–Meier Plotter and PrognoScan databases. The gene clusters of upregulated DEGs are involved mainly in cell division and cell proliferation, and the genes of downregulated DEGs primarily participate in the TGF-β signaling pathway and various metabolic processes. Via cross-validation of survival analysis, we identified four hub genes (AURKA, CDCA5, CEP55 and UBE2C) that correlated with ovarian cancer OS and PFS, which derived from the upregulated DEGs. Patients with these four hub genes trended toward worse OS and PFS than patients with low expression. Unfortunately, no significantly prognosis-related genes were detected among downregulated clusters. The mRNA expression of these four genes were analysed using the Oncomine and GEPIA databases, and the result revealed that the mRNA expression of AURKA,CDCA5,CEP55 and UBE2C was greatly upregulated in OC tissues compare with normal tissues. The gene set/pathway primarily showed alterations in amplification and deep deletion, and correlation analysis indicated significant positive correlations between AURKA, CDCA5, CEP55 and UBE2C. Nevertheless, for clarifying the protein expression levels of the four prognostic genes, the staining of the immunohistochemistry (IHC) were obtained base on the Human Protein Atlas, and was showed the proteins levels of these four genes was significantly elevated in patients with OC. Our results revealed that these four hub genes may mediate ovarian cancer development and have valuable clinical potential as prognostic biomarkers for OC patients.

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Cep55 promotes cytokinesis of neural progenitors but is dispensable for most mammalian cell divisions

Cited by 42 publications

References 71 publications

Loss of Coiled-Coil Protein Cep55 Impairs Neural Stem Cell Abscission and Results in p53-Dependent Apoptosis in Developing Cortex

Loss of Coiled-Coil Protein Cep55 Impairs Neural Stem Cell Abscission and Results in p53-Dependent Apoptosis in Developing Cortex

Abscission Checkpoint Bodies Reveal a New Facet of Abscission Checkpoint Control

Identification of Candidate Biomarkers Associated with Ovarian Cancer Progression and Prognosis by Integrated Microarray Analysis

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