NuSAP is essential for chromatin-induced spindle formation during early embryogenesis

Bosch, An Vanden; Raemaekers, Tim; Denayer, Sarah; Torrekens, Sophie; Smets, Nico; Moermans, Karen; Dewerchin, Mieke; Carmeliet, Peter; Carmeliet, Geert

doi:10.1242/dev.059303

Cited by 10 publications

(11 citation statements)

References 20 publications

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“…Moreover, E2F family members are targets of signaling through EGFRs 93 [95][96][97][98][99] and are known to be transcriptionally induced by E2Fs [100][101][102][103] . Strikingly, with the exception of E2F3, all were consistently repressed in response to SARS2 infection (Fig.…”

Section: Hypothesis Generation Use Case 4: Sars2 Repression Of E2f Famentioning

confidence: 99%

Consensus transcriptional regulatory networks of coronavirus-infected human cells

Ochsner

Pillich

McKenna

2020

Preprint

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15Identifying transcriptional responses that are most consistently associated with 16 experimental coronavirus (CoV) infection can help illuminate human cellular signaling 17 pathways impacted by CoV infection. Here, we distilled over 3,000,000 data points from 18 publically archived CoV infection transcriptomic datasets into consensus regulatory 19 signatures, or consensomes, that rank genes based on their transcriptional 20 responsiveness to infection of human cells by MERS, SARS-CoV-1 and SARS-CoV-2 21 subtypes. We computed overlap between genes with elevated rankings in the CoV 22 consensomes against those from transcriptomic and ChIP-Seq consensomes for nearly 23 880 cellular signaling pathway nodes. Validating the CoV infection consensomes, we 24 identified robust overlap between their highly ranked genes and high confidence targets 25 of signaling pathway nodes with known roles in CoV infection. We then developed a 26 series of use cases that illustrate the utility of the CoV consensomes for hypothesis 27 generation around mechanistic aspects of the cellular response to CoV infection. We 28 make the CoV infection consensomes and their universe of underlying data points freely 29 accessible through the Signaling Pathways Project web knowledgebase. 30 31 65 points in a series of use cases illuminates previously uncharacterized intersections 66 between CoV infection and human cellular signaling pathways. The CoV infection 67 consensome and its underlying datasets provide researchers with a unique and freely 68 accessible framework within which to generate and pressure test hypotheses around 69 human cellular signaling pathways impacted by CoV infection.70 71 72 73 5 Results 74Generation of the CoV consensomes 75 We first set out to generate a set of consensomes ranking human genes based on the 76 frequency of their significant differential expression in response to infection by MERS, 77 SARS1 and SARS2 CoVs. To do this we searched the Gene Expression Omnibus 78 (GEO) and ArrayExpress databases to identify datasets involving infection of human 79 cells by these species. From this initial collection of datasets, we next carried out a 80 three step quality control check as previously described (Ochsner et al., 2019), yielding 81 a total of 3,041,047 million data points in 111 experiments from 25 independent CoV 82 infection transcriptomic datasets (Supplementary information, Section 1). Using these 83 curated datasets, we next generated consensomes for each CoV species, as well as 84 one ranking genes across all CoV infection experiments (ALL CoV). As a reference 85 consensome for a virus whose transcriptional impact on human cells has been studied 86 in depth, we also generated a consensome for human influenza A virus (IAV) infection. 87The Supplementary information files contain the full human ALL CoV (Section 2), MERS 88 (Section 3), SARS1 (Section 4), SARS2 (Section 5) and IAV (Section 6) infection 89 transcriptomic consensomes. To assist researchers in inferring transcriptional regulation 90 of sig...

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Section: Hypothesis Generation Use Case 4: Sars2 Repression Of E2f Famentioning

confidence: 99%

Consensus transcriptional regulatory networks of coronavirus-infected human cells

Ochsner

Pillich

McKenna

2020

Preprint

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“…Nucleolar and spindle-associated protein 1 (NUSAP1) 3 is a mitotic phosphoprotein that binds microtubules and has been implicated in cell division (1)(2)(3)(4)(5)(6). NUSAP1 is highly conserved among higher eukaryotes and genetic knock-out in mice is embryonic lethal due to chromosome segregation defects (4). NUSAP1 is overexpressed in numerous malignancies, and high levels correlate with poor prognosis in aggressive triple-negative breast cancer (7).…”

Section: The Mitotic Spindle Is Composed Of Dynamic Microtubules and mentioning

confidence: 99%

Nucleolar and spindle-associated protein 1 (NUSAP1) interacts with a SUMO E3 ligase complex during chromosome segregation

Mills

Suzuki²,

Arceci

et al. 2017

Journal of Biological Chemistry

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The mitotic spindle is composed of dynamic microtubules and associated proteins that together direct chromosome movement during mitosis. The spindle plays a vital role in accurate chromosome segregation fidelity and is a therapeutic target in cancer. Nevertheless, the molecular mechanisms by which many spindle-associated proteins function remains unknown. The cleolar andpindle-ssociated rotein NUSAP1 is a microtubule-binding protein implicated in spindle stability and chromosome segregation. We show here that NUSAP1 localizes to dynamic spindle microtubules in a unique chromosome-centric pattern, in the vicinity of overlapping microtubules, during metaphase and anaphase of mitosis. Mass spectrometry-based analysis of endogenous NUSAP1 interacting proteins uncovered a cell cycle-regulated interaction between the RanBP2-RanGAP1-UBC9 SUMO E3 ligase complex and NUSAP1. Like NUSAP1 depletion, RanBP2 depletion impaired the response of cells to the microtubule poison Taxol. NUSAP1 contains a conserved SAP domain (SAF-A/B, Acinus, and PIAS). SAP domains are common among many other SUMO E3s, and are implicated in substrate recognition and ligase activity. We speculate that NUSAP1 contributes to accurate chromosome segregation by acting as a co-factor for RanBP2-RanGAP1-UBC9 during cell division.

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“…Importin-a and/or importin-b, importin 7 (Ribbeck et al, 2006;Ribbeck et al, 2007) Interacts with chromosomes and MTs (Ribbeck et al, 2006;Ribbeck et al, 2007) Early embryonic lethality (Vanden Bosch et al, 2010) Spindle organization NUMA1 Importin-b (Nachury et al, 2001;Wiese et al, 2001) Pole focusing (Haren et al, 2009;Merdes et al, 2000;Merdes et al, 1996;Silk et al, 2009) n.d.…”

Section: Nusap1mentioning

confidence: 99%

Microtubule assembly during mitosis – from distinct origins to distinct functions?

Meunier

Vernos

2012

Journal of Cell Science

125

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SummaryThe mitotic spindle is structurally and functionally defined by its main component, the microtubules (MTs). The MTs making up the spindle have various functions, organization and dynamics: astral MTs emanate from the centrosome and reach the cell cortex, and thus have a major role in spindle positioning; interpolar MTs are the main constituent of the spindle and are key for the establishment of spindle bipolarity, chromosome congression and central spindle assembly; and kinetochore-fibers are MT bundles that connect the kinetochores with the spindle poles and segregate the sister chromatids during anaphase. The duplicated centrosomes were long thought to be the origin of all of these MTs. However, in the last decade, a number of studies have contributed to the identification of noncentrosomal pathways that drive MT assembly in dividing cells. These pathways are now known to be essential for successful spindle assembly and to participate in various processes such as K-fiber formation and central spindle assembly. In this Commentary, we review the recent advances in the field and discuss how different MT assembly pathways might cooperate to successfully form the mitotic spindle.

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NuSAP is essential for chromatin-induced spindle formation during early embryogenesis

Cited by 10 publications

References 20 publications

Consensus transcriptional regulatory networks of coronavirus-infected human cells

Consensus transcriptional regulatory networks of coronavirus-infected human cells

Nucleolar and spindle-associated protein 1 (NUSAP1) interacts with a SUMO E3 ligase complex during chromosome segregation

Microtubule assembly during mitosis – from distinct origins to distinct functions?

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