scholarly journals Spatiotemporal expression of regulatory kinases directs the transition from mitotic growth to cellular morphogenesis

2020 ◽  
Author(s):  
Shuo Yang ◽  
Jennifer McAdow ◽  
Yingqiu Du ◽  
Jennifer Trigg ◽  
Paul Taghert ◽  
...  
Keyword(s):  
Aurora B ◽  
Cell Cycle Exit ◽  
Mitotic Entry ◽  
Regulatory Modules ◽  
Mitotic Kinase ◽  
Back Seat ◽  
Spatiotemporal Expression ◽  
Cellular Morphogenesis ◽  
Regulatory Module ◽  
Kinase Expression

Abstract Embryogenesis depends on a tightly regulated balance between mitotic growth, differentiation, and morphogenesis. Understanding how the embryo uses a relatively small number of proteins to transition between growth and morphogenesis is a central question of developmental biology, but the mechanisms controlling mitosis and differentiation are considered to be fundamentally distinct. Here we show the mitotic kinase Polo, which regulates all steps of mitosis from mitotic entry to cytokinesis, also directs cellular morphogenesis after cell cycle exit. In mitotic cells, Aurora B (AurB) activates Polo to control a cytoskeletal regulatory module that directs cytokinesis. In the post-mitotic mesoderm of late stage embryos, the control of Polo activation transitions to the uncharacterized kinase Back Seat Driver (Bsd), where Bsd activates Polo to direct muscle morphogenesis. The transition between mitotic growth and morphogenesis is accomplished through the spatiotemporal transcriptional regulation of AurB and Bsd. The functions of Bsd and Polo are conserved, arguing that regulating kinase expression to activate cytoskeletal regulatory modules is a widely used strategy to direct cellular morphogenesis.

scholarly journals Spatiotemporal expression of regulatory kinases directs the transition from mitotic growth to cellular morphogenesis

2020 ◽  
Author(s):  
Shuo Yang ◽  
Jennifer McAdow ◽  
Yingqiu Du ◽  
Jennifer Trigg ◽  
Paul H. Taghert ◽  
...  
Keyword(s):  
Aurora B ◽  
Cell Cycle Exit ◽  
Mitotic Entry ◽  
Regulatory Modules ◽  
Mitotic Kinase ◽  
Back Seat ◽  
Spatiotemporal Expression ◽  
Cellular Morphogenesis ◽  
Regulatory Module ◽  
Kinase Expression

SummaryEmbryogenesis depends on a tightly regulated balance between mitotic growth, differentiation, and morphogenesis. Understanding how the embryo uses a relatively small number of proteins to transition between growth and morphogenesis is a central question of developmental biology, but the mechanisms controlling mitosis and differentiation are considered to be fundamentally distinct. Here we show the mitotic kinase Polo, which regulates all steps of mitosis from mitotic entry to cytokinesis [1–3], also directs cellular morphogenesis after cell cycle exit. In mitotic cells, Aurora B (AurB) activates Polo to control a cytoskeletal regulatory module that directs cytokinesis [4–6]. In the post-mitotic mesoderm of late stage embryos, the control of Polo activation transitions to the uncharacterized kinase Back Seat Driver (Bsd), where Bsd activates Polo to direct muscle morphogenesis. The transition between mitotic growth and morphogenesis is accomplished through the spatiotemporal transcriptional regulation of AurB and Bsd. The functions of Bsd and Polo are conserved, arguing that regulating kinase expression to activate cytoskeletal regulatory modules is a widely used strategy to direct cellular morphogenesis.

scholarly journals The characteristics of circRNA as competing endogenous RNA in pathogenesis of acute myeloid leukemia

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Siyuan Zhang
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Expression Profiles ◽  
Gene Expression Omnibus ◽  
The Novel ◽  
Competing Endogenous Rna ◽  
Regulatory Modules ◽  
Cerna Network ◽  
Regulatory Module ◽  
Acute Myeloid

Abstract Background As one of the novel molecules, circRNA has been identified closely involved in the pathogenesis of many diseases. However, the function of circRNA in acute myeloid leukemia (AML) still remains unknown. Methods In the current study, the RNA expression profiles were obtained from Gene Expression Omnibus (GEO) datasets. The differentially expressed RNAs were identified using R software and the competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed to identify the candidate circRNA-mediated aberrant signaling pathways. The hub genes were identified by MCODE and CytoHubba plugins of Cytoscape, and then a subnetwork regulatory module was established. Results A total of 27 circRNA-miRNA pairs and 208 miRNA-mRNA pairs, including 12 circRNAs, 24 miRNAs and 112 mRNAs were included in the ceRNA network. Subsequently, a subnetwork, including 4 circRNAs, 5 miRNAs and 6 mRNAs, was established based on related circRNA-miRNA-mRNA regulatory modules. Conclusions In summary, this work analyzes the characteristics of circRNA as competing endogenous RNA in AML pathogenesis, which would provide hints for developing novel prognostic, diagnostic and therapeutic strategy for AML.

scholarly journals Dog colour patterns explained by modular promoters of ancient canid origin

2021 ◽  
Author(s):  
Danika L. Bannasch ◽  
Christopher B. Kaelin ◽  
Anna Letko ◽  
Robert Loechel ◽  
Petra Hug ◽  
...  
Keyword(s):  
Colour Pattern ◽  
Hair Cycle ◽  
Temporal And Spatial Distribution ◽  
Multiple Alleles ◽  
Haplotype Combination ◽  
Regulatory Modules ◽  
Regulatory Module ◽  
Temporal And Spatial ◽  
Selection For ◽  
Colour Patterns

AbstractDistinctive colour patterns in dogs are an integral component of canine diversity. Colour pattern differences are thought to have arisen from mutation and artificial selection during and after domestication from wolves but important gaps remain in understanding how these patterns evolved and are genetically controlled. In other mammals, variation at the ASIP gene controls both the temporal and spatial distribution of yellow and black pigments. Here, we identify independent regulatory modules for ventral and hair cycle ASIP expression, and we characterize their action and evolutionary origin. Structural variants define multiple alleles for each regulatory module and are combined in different ways to explain five distinctive dog colour patterns. Phylogenetic analysis reveals that the haplotype combination for one of these patterns is shared with Arctic white wolves and that its hair cycle-specific module probably originated from an extinct canid that diverged from grey wolves more than 2 million years ago. Natural selection for a lighter coat during the Pleistocene provided the genetic framework for widespread colour variation in dogs and wolves.

scholarly journals Oncogenic MYC amplifies mitotic perturbations

Open Biology ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 190136 ◽  
Author(s):  
Samantha Littler ◽  
Olivia Sloss ◽  
Bethany Geary ◽  
Andrew Pierce ◽  
Anthony D. Whetton ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Chromosome Instability ◽  
Ros Production ◽  
Mitotic Entry ◽  
Multiple Networks ◽  
Mitotic Kinase ◽  
Dependent Processes ◽  
Ability To Drive ◽  
Oncogenic Transcription Factor

The oncogenic transcription factor MYC modulates vast arrays of genes, thereby influencing numerous biological pathways including biogenesis, metabolism, proliferation, apoptosis and pluripotency. When deregulated, MYC drives genomic instability via several mechanisms including aberrant proliferation, replication stress and ROS production. Deregulated MYC also promotes chromosome instability, but less is known about how MYC influences mitosis. Here, we show that deregulating MYC modulates multiple aspects of mitotic chromosome segregation. Cells overexpressing MYC have altered spindle morphology, take longer to align their chromosomes at metaphase and enter anaphase sooner. When challenged with a variety of anti-mitotic drugs, cells overexpressing MYC display more anomalies, the net effect of which is increased micronuclei, a hallmark of chromosome instability. Proteomic analysis showed that MYC modulates multiple networks predicted to influence mitosis, with the mitotic kinase PLK1 identified as a central hub. In turn, we show that MYC modulates several PLK1-dependent processes, namely mitotic entry, spindle assembly and SAC satisfaction. These observations thus underpin the pervasive nature of oncogenic MYC and provide a mechanistic rationale for MYC's ability to drive chromosome instability.

scholarly journals Mitosis-specific MPM-2 phosphorylation of DNA topoisomerase IIα is regulated directly by protein phosphatase 2A

2007 ◽  
Vol 403 (2) ◽  
pp. 235-242 ◽  
Author(s):  
Alexandre E. Escargueil ◽  
Annette K. Larsen
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Fine Tuning ◽  
Classical Pathway ◽  
Complete Disappearance ◽  
Topoisomerase Iiα ◽  
Mitotic Entry ◽  
Mitotic Kinase ◽  
Short Term Exposure ◽  
Phosphatase 2A

Recent results suggest a role for topoIIα (topoisomerase IIα) in the fine-tuning of mitotic entry. Mitotic entry is accompanied by the formation of specific phosphoepitopes such as MPM-2 (mitotic protein monoclonal 2) that are believed to control mitotic processes. Surprisingly, the MPM-2 kinase of topoIIα was identified as protein kinase CK2, otherwise known as a constitutive interphase kinase. This suggested the existence of alternative pathways for the creation of mitotic phosphoepitopes, different from the classical pathway where the substrate is phosphorylated by a mitotic kinase. In the present paper, we report that topoIIα is co-localized with both CK2 and PP2A (protein phosphatase 2A) during interphase. Simultaneous incubation of purified topoIIα with CK2 and PP2A had minimal influence on the total phosphorylation levels of topoIIα, but resulted in complete disappearance of the MPM-2 phosphoepitope owing to opposite sequence preferences of CK2 and PP2A. Accordingly, short-term exposure of interphase cells to okadaic acid, a selective PP2A inhibitor, was accompanied by the specific appearance of the MPM-2 phosphoepitope on topoIIα. During early mitosis, PP2A was translocated from the nucleus, while CK2 remained in the nucleus until pro-metaphase thus permitting the formation of the MPM-2 phosphoepitope. These results underline the importance of protein phosphatases as an alternative way of creating cell-cycle-specific phosphoepitopes.

scholarly journals A Mitotic GlcNAcylation/Phosphorylation Signaling Complex Alters the Posttranslational State of the Cytoskeletal Protein Vimentin

2008 ◽  
Vol 19 (10) ◽  
pp. 4130-4140 ◽  
Author(s):  
Chad Slawson ◽  
T. Lakshmanan ◽  
Spencer Knapp ◽  
Gerald W. Hart
Keyword(s):  
Cell Cycle ◽  
Protein Modification ◽  
Cell Cycle Progression ◽  
Stress Hormones ◽  
Aurora B ◽  
Intermediate Filament Protein ◽  
Mitotic Kinase ◽  
Transient Complex ◽  
M Phase ◽  
Mitotic Phosphorylation

O-linked β-N-acetylglucosamine (O-GlcNAc) is a highly dynamic intracellular protein modification responsive to stress, hormones, nutrients, and cell cycle stage. Alterations in O-GlcNAc addition or removal (cycling) impair cell cycle progression and cytokinesis, but the mechanisms are not well understood. Here, we demonstrate that the enzymes responsible for O-GlcNAc cycling, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) are in a transient complex at M phase with the mitotic kinase Aurora B and protein phosphatase 1. OGT colocalized to the midbody during telophase with Aurora B. Furthermore, these proteins coprecipitated with each other in a late mitotic extract. The complex was stable under Aurora inhibition; however, the total cellular levels of O-GlcNAc were increased and the localization of OGT was decreased at the midbody after Aurora inhibition. Vimentin, an intermediate filament protein, is an M phase substrate for both Aurora B and OGT. Overexpression of OGT or OGA led to defects in mitotic phosphorylation on multiple sites, whereas OGT overexpression increased mitotic GlcNAcylation of vimentin. OGA inhibition caused a decrease in vimentin late mitotic phosphorylation but increased GlcNAcylation. Together, these data demonstrate that the O-GlcNAc cycling enzymes associate with kinases and phosphatases at M phase to regulate the posttranslational status of vimentin.

scholarly journals Bub1, Sgo1, and Mps1 mediate a distinct pathway for chromosome biorientation in budding yeast

2011 ◽  
Vol 22 (9) ◽  
pp. 1473-1485 ◽  
Author(s):  
Zuzana Storchová ◽  
Justin S. Becker ◽  
Nicolas Talarek ◽  
Sandra Kögelsberger ◽  
David Pellman
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Budding Yeast ◽  
Spindle Pole ◽  
Growth Defect ◽  
Aurora B ◽  
Mitotic Kinase ◽  
Sister Chromatids ◽  
Chromosome Alignment ◽  
Chromosomal Passenger

The conserved mitotic kinase Bub1 performs multiple functions that are only partially characterized. Besides its role in the spindle assembly checkpoint and chromosome alignment, Bub1 is crucial for the kinetochore recruitment of multiple proteins, among them Sgo1. Both Bub1 and Sgo1 are dispensable for growth of haploid and diploid budding yeast, but they become essential in cells with higher ploidy. We find that overexpression of SGO1 partially corrects the chromosome segregation defect of bub1Δ haploid cells and restores viability to bub1Δ tetraploid cells. Using an unbiased high-copy suppressor screen, we identified two members of the chromosomal passenger complex (CPC), BIR1 (survivin) and SLI15 (INCENP, inner centromere protein), as suppressors of the growth defect of both bub1Δ and sgo1Δ tetraploids, suggesting that these mutants die due to defects in chromosome biorientation. Overexpression of BIR1 or SLI15 also complements the benomyl sensitivity of haploid bub1Δ and sgo1Δ cells. Mutants lacking SGO1 fail to biorient sister chromatids attached to the same spindle pole (syntelic attachment) after nocodazole treatment. Moreover, the sgo1Δ cells accumulate syntelic attachments in unperturbed mitoses, a defect that is partially corrected by BIR1 or SLI15 overexpression. We show that in budding yeast neither Bub1 nor Sgo1 is required for CPC localization or affects Aurora B activity. Instead we identify Sgo1 as a possible partner of Mps1, a mitotic kinase suggested to have an Aurora B–independent function in establishment of biorientation. We found that Sgo1 overexpression rescues defects caused by metaphase inactivation of Mps1 and that Mps1 is required for Sgo1 localization to the kinetochore. We propose that Bub1, Sgo1, and Mps1 facilitate chromosome biorientation independently of the Aurora B–mediated pathway at the budding yeast kinetochore and that both pathways are required for the efficient turnover of syntelic attachments.

scholarly journals Mitotic Kinase Expression and Colorectal Cancer Progression

1999 ◽  
Vol 91 (13) ◽  
pp. 1160-1162 ◽  
Author(s):  
H. Katayama ◽  
T. Ota ◽  
F. Jisaki ◽  
Y. Ueda ◽  
T. Tanaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Mitotic Kinase ◽  
Colorectal Cancer Progression ◽  
Kinase Expression

scholarly journals DNA replication checkpoint control of Wee1 stability by vertebrate Hsl7

2004 ◽  
Vol 167 (5) ◽  
pp. 841-849 ◽  
Author(s):  
Ayumi Yamada ◽  
Brad Duffy ◽  
Jennifer A. Perry ◽  
Sally Kornbluth
Keyword(s):  
Dna Replication ◽  
Cell Cycle Control ◽  
Checkpoint Control ◽  
Checkpoint Activation ◽  
Replication Checkpoint ◽  
Synthetic Lethal ◽  
Mitotic Entry ◽  
Regulatory Module ◽  
Dna Replication Checkpoint ◽  
Control Modules

G2/M checkpoints prevent mitotic entry upon DNA damage or replication inhibition by targeting the Cdc2 regulators Cdc25 and Wee1. Although Wee1 protein stability is regulated by DNA-responsive checkpoints, the vertebrate pathways controlling Wee1 degradation have not been elucidated. In budding yeast, stability of the Wee1 homologue, Swe1, is controlled by a regulatory module consisting of the proteins Hsl1 and Hsl7 (histone synthetic lethal 1 and 7), which are targeted by the morphogenesis checkpoint to prevent Swe1 degradation when budding is inhibited. We report here the identification of Xenopus Hsl7 as a positive regulator of mitosis that is controlled, instead, by an entirely distinct checkpoint, the DNA replication checkpoint. Although inhibiting Hsl7 delayed mitosis, Hsl7 overexpression overrode the replication checkpoint, accelerating Wee1 destruction. Replication checkpoint activation disrupted Hsl7–Wee1 interactions, but binding was restored by active polo-like kinase. These data establish Hsl7 as a component of the replication checkpoint and reveal that similar cell cycle control modules can be co-opted for use by distinct checkpoints in different organsims.

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