Abstract 2987: A critical role of translocated promoter region (Tpr) in chromosome segregation and cell division in cancer

2011 ◽  
Author(s):  
Tatsuyoshi Funasaka ◽  
Hiroshi Nakano ◽  
Richard Wong
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Promoter Region ◽  
Critical Role

scholarly journals WNT/β-catenin-suppressed FTO expression increases m6A of c-Myc mRNA to promote tumor cell glycolysis and tumorigenesis

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xueying Yang ◽  
Fei Shao ◽  
Dong Guo ◽  
Wei Wang ◽  
Juhong Wang ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Promoter Region ◽  
Critical Role ◽  
Mrna Translation ◽  
Poor Survival ◽  
Subsequent Increase ◽  
Critical Pathways ◽  
Number Of Genes ◽  
Promote Tumor Cell

AbstractFTO removes the N6-methyladenosine (m6A) modification from genes and plays a critical role in cancer development. However, the mechanisms underlying the regulation of FTO and its subsequent impact on the regulation of the epitranscriptome remain to be further elucidated. Here, we demonstrate that FTO expression is downregulated and inversely correlated with poor survival of lung adenocarcinoma patients. Mechanistically, Wnt signaling induces the binding of EZH2 to β-catenin. This protein complex binds to the LEF/TCF-binding elements at the promoter region of FTO, where EZH2 enhances H3K27me3 and inhibits FTO expression. Downregulated FTO expression substantially enhances the m6A levels in the mRNAs of a large number of genes in critical pathways, particularly metabolic pathway genes, such as MYC. Enhanced m6A levels on MYC mRNA recruit YTHDF1 binding, which promotes MYC mRNA translation and a subsequent increase in glycolysis and proliferation of tumor cells and tumorigenesis. Our findings uncovered a critical mechanism of epitranscriptome regulation by Wnt/β-catenin-mediated FTO downregulation and underscored the role of m6A modifications of MYC mRNA in regulating tumor cell glycolysis and growth.

fumble Encodes a Pantothenate Kinase Homolog Required for Proper Mitosis and Meiosis in Drosophila melanogaster

Genetics ◽  
2001 ◽  
Vol 157 (3) ◽  
pp. 1267-1276
Author(s):  
Katayoun Afshar ◽  
Pierre Gönczy ◽  
Stephen DiNardo ◽  
Steven A Wasserman
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Cell Division Cycle ◽  
Protein Isoforms ◽  
Pantothenate Kinase ◽  
Male Germline ◽  
Dividing Cells ◽  
Mutant Cells ◽  
Mitosis And Meiosis

Abstract A number of fundamental processes comprise the cell division cycle, including spindle formation, chromosome segregation, and cytokinesis. Our current understanding of these processes has benefited from the isolation and analysis of mutants, with the meiotic divisions in the male germline of Drosophila being particularly well suited to the identification of the required genes. We show here that the fumble (fbl) gene is required for cell division in Drosophila. We find that dividing cells in fbl-deficient testes exhibit abnormalities in bipolar spindle organization, chromosome segregation, and contractile ring formation. Cytological analysis of larval neuroblasts from null mutants reveals a reduced mitotic index and the presence of polyploid cells. Molecular analysis demonstrates that fbl encodes three protein isoforms, all of which contain a domain with high similarity to the pantothenate kinases of A. nidulans and mouse. The largest Fumble isoform is dispersed in the cytoplasm during interphase, concentrates around the spindle at metaphase, and localizes to the spindle midbody at telophase. During early embryonic development, the protein localizes to areas of membrane deposition and/or rearrangement, such as the metaphase and cellularization furrows. Given the role of pantothenate kinase in production of Coenzyme A and in phospholipid biosynthesis, this pattern of localization is suggestive of a role for fbl in membrane synthesis. We propose that abnormalities in synthesis and redistribution of membranous structures during the cell division cycle underlie the cell division defects in fbl mutant cells.

scholarly journals The Drosophila Kinesin-like Protein KLP67A Is Essential for Mitotic and Male Meiotic Spindle Assembly

2004 ◽  
Vol 15 (1) ◽  
pp. 121-131 ◽  
Author(s):  
Rita Gandhi ◽  
Silvia Bonaccorsi ◽  
Diana Wentworth ◽  
Stephen Doxsey ◽  
Maurizio Gatti ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Mutational Analysis ◽  
Spindle Assembly ◽  
Male Meiosis ◽  
Meiotic Spindle ◽  
Drosophila Cell ◽  
Centrosome Separation ◽  
Mutant Cells

We have performed a mutational analysis together with RNA interference to determine the role of the kinesin-like protein KLP67A in Drosophila cell division. During both mitosis and male meiosis, Klp67A mutations cause an increase in MT length and disrupt discrete aspects of spindle assembly, as well as cytokinesis. Mutant cells exhibit greatly enlarged metaphase spindle as a result of excessive MT polymerization. The analysis of both living and fixed cells also shows perturbations in centrosome separation, chromosome segregation, and central spindle assembly. These data demonstrate that the MT plus end-directed motor KLP67A is essential for spindle assembly during mitosis and male meiosis and suggest that the regulation of MT plus-end polymerization is a key determinant of spindle architecture throughout cell division.

scholarly journals CENP-C is a blueprint for constitutive centromere–associated network assembly within human kinetochores

2015 ◽  
Vol 210 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Kerstin Klare ◽  
John R. Weir ◽  
Federica Basilico ◽  
Tomasz Zimniak ◽  
Lucia Massimiliano ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
The Other ◽  
Microtubule Binding ◽  
Kinetochore Assembly ◽  
Binding Interface ◽  
Other Hand ◽  
Spindle Microtubules ◽  
Data Point

Kinetochores are multisubunit complexes that assemble on centromeres to bind spindle microtubules and promote faithful chromosome segregation during cell division. A 16-subunit complex named the constitutive centromere–associated network (CCAN) creates the centromere–kinetochore interface. CENP-C, a CCAN subunit, is crucial for kinetochore assembly because it links centromeres with the microtubule-binding interface of kinetochores. The role of CENP-C in CCAN organization, on the other hand, had been incompletely understood. In this paper, we combined biochemical reconstitution and cellular investigations to unveil how CENP-C promotes kinetochore targeting of other CCAN subunits. The so-called PEST domain in the N-terminal half of CENP-C interacted directly with the four-subunit CCAN subcomplex CENP-HIKM. We identified crucial determinants of this interaction whose mutation prevented kinetochore localization of CENP-HIKM and of CENP-TW, another CCAN subcomplex. When considered together with previous observations, our data point to CENP-C as a blueprint for kinetochore assembly.

scholarly journals Stable inheritance of Sinorhizobium meliloti cell growth polarity requires an FtsN-like protein and an amidase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Elizaveta Krol ◽  
Lisa Stuckenschneider ◽  
Joana M. Kästle Silva ◽  
Peter L. Graumann ◽  
Anke Becker
Keyword(s):  
Cell Division ◽  
Cell Polarity ◽  
Chromosome Segregation ◽  
Cell Elongation ◽  
Sinorhizobium Meliloti ◽  
Growth Zone ◽  
Cell Pole ◽  
Growth Polarity ◽  
Selection Of

AbstractIn Rhizobiales bacteria, such as Sinorhizobium meliloti, cell elongation takes place only at new cell poles, generated by cell division. Here, we show that the role of the FtsN-like protein RgsS in S. meliloti extends beyond cell division. RgsS contains a conserved SPOR domain known to bind amidase-processed peptidoglycan. This part of RgsS and peptidoglycan amidase AmiC are crucial for reliable selection of the new cell pole as cell elongation zone. Absence of these components increases mobility of RgsS molecules, as well as abnormal RgsS accumulation and positioning of the growth zone at the old cell pole in about one third of the cells. These cells with inverted growth polarity are able to complete the cell cycle but show partially impaired chromosome segregation. We propose that amidase-processed peptidoglycan provides a landmark for RgsS to generate cell polarity in unipolarly growing Rhizobiales.

Mitotic spindle morphogenesis: Ran on the microtubule cytoskeleton and beyond

2006 ◽  
Vol 34 (5) ◽  
pp. 716-721 ◽  
Author(s):  
B. Goodman ◽  
Y. Zheng
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Microtubule Assembly ◽  
Microtubule Organization ◽  
Spindle Matrix ◽  
Small G Protein ◽  
Important Regulator

Assembly and disassembly of the mitotic spindle are essential for both chromosome segregation and cell division. The small G-protein Ran has emerged as an important regulator of spindle assembly. In this review, we look at the role of Ran in different aspects of spindle assembly, including its effects on microtubule assembly dynamics and microtubule organization. In addition, we examine the possibility of a spindle matrix and the role Ran might play in such a structure.

scholarly journals Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly

2009 ◽  
Vol 185 (5) ◽  
pp. 859-874 ◽  
Author(s):  
Ying Wai Chan ◽  
Luca L. Fava ◽  
Andreas Uldschmid ◽  
Michael H.A. Schmitz ◽  
Daniel W. Gerlich ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Critical Role ◽  
Spindle Orientation ◽  
Aurora B ◽  
C Elegans ◽  
Spindle Rotation ◽  
Mitotic Control ◽  
New Protein

Mitotic spindle formation and chromosome segregation depend critically on kinetochore–microtubule (KT–MT) interactions. A new protein, termed Spindly in Drosophila and SPDL-1 in C. elegans, was recently shown to regulate KT localization of dynein, but depletion phenotypes revealed striking differences, suggesting evolutionarily diverse roles of mitotic dynein. By characterizing the function of Spindly in human cells, we identify specific functions for KT dynein. We show that localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B. hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment. Moreover, depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein. However, in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs. Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation.

scholarly journals Role for polo-like kinase 4 in mediation of cytokinesis

2019 ◽  
Vol 116 (23) ◽  
pp. 11309-11318 ◽  
Author(s):  
Michael F. Press ◽  
Bin Xie ◽  
Simon Davenport ◽  
Yu Zhou ◽  
Roberta Guzman ◽  
...  
Keyword(s):  
Cell Division ◽  
Kinase Activity ◽  
Critical Role ◽  
Mitotic Catastrophe ◽  
Centrosome Duplication ◽  
Cleavage Furrow ◽  
Molecule Inhibitor ◽  
Colorectal Cancer Cells ◽  
Spindle Midzone

The mitotic protein polo-like kinase 4 (PLK4) plays a critical role in centrosome duplication for cell division. By using immunofluorescence, we confirm that PLK4 is localized to centrosomes. In addition, we find that phospho-PLK4 (pPLK4) is cleaved and distributed to kinetochores (metaphase and anaphase), spindle midzone/cleavage furrow (anaphase and telophase), and midbody (cytokinesis) during cell division in immortalized epithelial cells as well as breast, ovarian, and colorectal cancer cells. The distribution of pPLK4 midzone/cleavage furrow and midbody positions pPLK4 to play a functional role in cytokinesis. Indeed, we found that inhibition of PLK4 kinase activity with a small-molecule inhibitor, CFI-400945, prevents translocation to the spindle midzone/cleavage furrow and prevents cellular abscission, leading to the generation of cells with polyploidy, increased numbers of duplicated centrosomes, and vulnerability to anaphase or mitotic catastrophe. The regulatory role of PLK4 in cytokinesis makes it a potential target for therapeutic intervention in appropriately selected cancers.

scholarly journals Impaired chromosome segregation results in sperms with excess centrosomes in emb-27APC6 mutant C. elegans

2018 ◽  
Author(s):  
Tomo Kondo ◽  
Akatsuki Kimura
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Anaphase Promoting Complex ◽  
C Elegans ◽  
Secondary Spermatocyte ◽  
Centrosome Separation ◽  
A Subunit ◽  
Excess Number

AbstractThe anaphase-promoting complex (APC) is a major regulator of chromosome segregation and is implicated in centriole engagement, whose de-regulation causes abnormal number of centrosomes. The emb-27 gene in C. elegans encodes a subunit of APC. The paternal emb-27 mutant was reported to show cell division with multiple furrows, suggesting the presence of excess centrosomes. In this study, we examined the number of centrosomes and the mechanism underlying de-regulation of centrosome number in emb-27 mutants. Our observations indicated excess centrosomes in emb-27 sperms, which resulted in zygotes with excess centrosomes. Further, the secondary spermatocyte of emb-27 produced reduced number of spermatids, which is likely the direct cause of the excess number of centrosomes per sperm. We propose that a chromosome segregation defect in emb-27 induced centrosome separation defect, resulting in reduced number of buds. Additionally, treatment with cytoskeletal inhibiting drugs indicated presence of three kinds of forces working in combination to move the centrosomes into the spermatids. The present study suggested a novel role of microtubule in the budding cytokinesis of spermatocytes.

scholarly journals Role of the Number of Microtubules in Chromosome Segregation during Cell Division

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0141305 ◽  
Author(s):  
Zsolt Bertalan ◽  
Zoe Budrikis ◽  
Caterina A. M. La Porta ◽  
Stefano Zapperi
Keyword(s):  
Cell Division ◽  
Chromosome Segregation
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