The C. elegans F-box/WD-repeat protein LIN-23 functions to limit cell division during development

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5071-5082 ◽  
Author(s):  
E.T. Kipreos ◽  
S.P. Gohel ◽  
E.M. Hedgecock
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Cell Cycle Regulators ◽  
Loss Of Function ◽  
Repeat Protein ◽  
C Elegans ◽  
Blast Cells ◽  
Wd Repeat ◽  
And Function

In multicellular eukaryotes, a complex program of developmental signals regulates cell growth and division by controlling the synthesis, activation and degradation of G(1) cell cycle regulators. Here we describe the lin-23 gene of Caenorhabditis elegans, which is required to restrain cell proliferation in response to developmental cues. In lin-23 null mutants, all postembryonic blast cells undergo extra divisions, creating supernumerary cells that can differentiate and function normally. In contrast to the inability to regulate the extent of blast cell division in lin-23 mutants, the timing of initial cell cycle entry of blast cells is not affected. lin-23 encodes an F-box/WD-repeat protein that is orthologous to the Saccharomyces cerevisiae gene MET30, the Drosophila melanogaster gene slmb and the human gene betaTRCP, all of which function as components of SCF ubiquitin-ligase complexes. Loss of function of the Drosophila slmb gene causes the growth of ectopic appendages in a non-cell autonomous manner. In contrast, lin-23 functions cell autonomously to negatively regulate cell cycle progression, thereby allowing cell cycle exit in response to developmental signals.

Organ-specific cell division abnormalities caused by mutation in a general cell cycle regulator inC. elegans

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2155-2165
Author(s):  
Ivana Kostić ◽  
Richard Roy
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Ectopic Expression ◽  
Cell Lineage ◽  
Intestinal Cells ◽  
Specific Cell ◽  
Cell Cycle Regulators ◽  
Loss Of Function ◽  
C Elegans ◽  
Cell Divisions

The precise control of cell division during development is pivotal for morphogenesis and the correct formation of tissues and organs. One important gene family involved in such control is the p21/p27/p57 class of negative cell cycle regulators. Loss of function of the C. elegans p27 homolog, cki-1, causes extra cell divisions in numerous tissues including the hypodermis, the vulva, and the intestine. We have sought to better understand how cell divisions are controlled upstream or in parallel to cki-1 in specific organs during C. elegans development. By taking advantage of the invariant cell lineage of C. elegans, we used an intestinal-specific GFP reporter in a screen to identify mutants that undergo cell division abnormalities in the intestinal lineage. We have isolated a mutant with twice the wild-type complement of intestinal cells, all of which arise during mid-embryogenesis. This mutant, called rr31, is a fully dominant, maternal-effect, gain-of-function mutation in the cdc-25.1 cell cycle phosphatase that sensitizes the intestinal lineage to an extra cell division. We showed that cdc-25.1 acts at the G1/S transition, as ectopic expression of CDC-25.1 caused entry into S phase in intestinal cells. In addition, we showed that the cdc-25.1(gf) requires cyclin E. The extra cell division defect was shown to be restricted to the E lineage and the E fate is necessary and sufficient to sensitize cells to this mutation.

scholarly journals Casein Kinase II is Required for Proper Cell Division and Acts as a Negative Regulator of Centrosome Duplication in C. elegans Embryos

2016 ◽  
Author(s):  
Jeffrey C. Medley ◽  
Megan M. Kabara ◽  
Michael D. Stubenvoll ◽  
Lauren E. DeMeyer ◽  
Mi Hye Song
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Casein Kinase Ii ◽  
Casein Kinase ◽  
Negative Regulator ◽  
Centrosome Duplication ◽  
Dependent Manner ◽  
C Elegans ◽  
Mother Centriole

Summary statementThe conserved protein kinase CK2 negatively regulates centrosome assembly and is required for proper cell cycle progression and cytokinesis in early C. elegans embryos.AbstractCentrosomes are the primary microtubule-organizing centers that orchestrate microtubule dynamics during the cell cycle. The correct number of centrosomes is pivotal for establishing bipolar mitotic spindles that ensure accurate segregation of chromosomes. Thus, centrioles must duplicate once per cell cycle, one daughter per mother centriole, the process of which requires highly coordinated actions among core factors and modulators. Protein phosphorylation is shown to regulate the stability, localization and activity of centrosome proteins. Here, we report the function of Casein Kinase II (CK2) in early C. elegans embryos. The catalytic subunit (KIN-3/CK2α) of CK2 localizes to nuclei, centrosomes and midbodies. Inactivating CK2 leads to cell division defects, including chromosome missegregation, cytokinesis failure and aberrant centrosome behavior. Furthermore, depletion or inhibiting kinase activity of CK2 results in elevated ZYG-1 levels at centrosomes, restoring centrosome duplication and embryonic viability to zyg-1 mutants. Our data suggest that CK2 functions in cell division and negatively regulates centrosome duplication in a kinase-dependent manner.

scholarly journals dally, a Drosophila member of the glypican family of integral membrane proteoglycans, affects cell cycle progression and morphogenesis via a Cyclin A-mediated process

2002 ◽  
Vol 115 (1) ◽  
pp. 123-130 ◽  
Author(s):  
Hiroshi Nakato ◽  
Bethany Fox ◽  
Scott B. Selleck
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Optic Lobe ◽  
Cyclin A ◽  
Cell Cycle Regulators ◽  
Late Prophase ◽  
Cycle Progression ◽  
Dividing Cells ◽  
Morphological Defects

division abnormally delayed (dally) encodes an integral membrane proteoglycan of the glypican family that affects a number of patterning events during both embryonic and larval development. Earlier studies demonstrated that Dally regulates cellular responses to Wingless (Wg) and Decapentaplegic (Dpp) in a tissue-specific manner, consistent with its proposed role as a growth factor co-receptor. dally mutants also display cell cycle progression defects in specific sets of dividing cells in the developing optic lobe and retina. The affected cells in the retina and lamina show delays in completion of the G2-M segment of the cell cycle. We have investigated the molecular basis of dally-mediated cell division defects by examining the genetic interactions between dally and known cell cycle regulators. Reductions in cyclin A but not cyclin B or string expression, suppress dally cell division defects in the optic lobe. cycA mutations also dominantly rescue many dally adult morphological defects including lethality, phenotypes that are unaffected by reducing cycB function. dally mutants show abnormal Cyclin A expression in the dividing cells affected, with appreciable levels of Cyclin A remaining in late prophase and metaphase, stages where Cyclin A is normally absent. Given that Dally is known to regulate the activity of secreted growth factors our findings suggest that extracellular cues influence the degradation of Cyclin A in a manner that controls cell cycle progression and ultimately, cell division patterning.

scholarly journals The Last Chance Saloon

2021 ◽  
Vol 9 ◽  
Author(s):  
Ye Hong ◽  
Hongtao Zhang ◽  
Anton Gartner
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Genome Integrity ◽  
Cycle Progression ◽  
Chromosome Fragmentation ◽  
C Elegans ◽  
Chromatin Bridges

Accurate chromosome segregation requires the removal of all chromatin bridges, which link chromosomes before cell division. When chromatin bridges fail to be removed, cell cycle progression may halt, or cytokinesis failure and ensuing polyploidization may occur. Conversely, the inappropriate severing of chromatin bridges leads to chromosome fragmentation, excessive genome instability at breakpoints, micronucleus formation, and chromothripsis. In this mini-review, we first describe the origins of chromatin bridges, the toxic processing of chromatin bridges by mechanical force, and the TREX1 exonuclease. We then focus on the abscission checkpoint (NoCut) which can confer a transient delay in cytokinesis progression to facilitate bridge resolution. Finally, we describe a recently identified mechanism uncovered in C. elegans where the conserved midbody associated endonuclease LEM-3/ANKLE1 is able to resolve chromatin bridges generated by various perturbations of DNA metabolism at the final stage of cell division. We also discuss how LEM-3 dependent chromatin bridge resolution may be coordinated with abscission checkpoint (NoCut) to achieve an error-free cleavage, therefore acting as a “last chance saloon” to facilitate genome integrity and organismal survival.

scholarly journals The Modular Circuitry of Apicomplexan Cell Division Plasticity

2021 ◽  
Vol 11 ◽  
Author(s):  
Marc-Jan Gubbels ◽  
Isabelle Coppens ◽  
Kourosh Zarringhalam ◽  
Manoj T. Duraisingh ◽  
Klemens Engelberg
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Parasite Species ◽  
Developmental Stages ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Apicomplexan Parasites ◽  
Secondary Messengers ◽  
Acting In Concert

The close-knit group of apicomplexan parasites displays a wide variety of cell division modes, which differ between parasites as well as between different life stages within a single parasite species. The beginning and endpoint of the asexual replication cycles is a ‘zoite’ harboring the defining apical organelles required for host cell invasion. However, the number of zoites produced per division round varies dramatically and can unfold in several different ways. This plasticity of the cell division cycle originates from a combination of hard-wired developmental programs modulated by environmental triggers. Although the environmental triggers and sensors differ between species and developmental stages, widely conserved secondary messengers mediate the signal transduction pathways. These environmental and genetic input integrate in division-mode specific chromosome organization and chromatin modifications that set the stage for each division mode. Cell cycle progression is conveyed by a smorgasbord of positively and negatively acting transcription factors, often acting in concert with epigenetic reader complexes, that can vary dramatically between species as well as division modes. A unique set of cell cycle regulators with spatially distinct localization patterns insert discrete check points which permit individual control and can uncouple general cell cycle progression from nuclear amplification. Clusters of expressed genes are grouped into four functional modules seen in all division modes: 1. mother cytoskeleton disassembly; 2. DNA replication and segregation (D&S); 3. karyokinesis; 4. zoite assembly. A plug-and-play strategy results in the variety of extant division modes. The timing of mother cytoskeleton disassembly is hard-wired at the species level for asexual division modes: it is either the first step, or it is the last step. In the former scenario zoite assembly occurs at the plasma membrane (external budding), and in the latter scenario zoites are assembled in the cytoplasm (internal budding). The number of times each other module is repeated can vary regardless of this first decision, and defines the modes of cell division: schizogony, binary fission, endodyogeny, endopolygeny.

scholarly journals ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
María Victoria Castro ◽  
Gastón Alexis Barbero ◽  
María Belén Villanueva ◽  
Luca Grumolato ◽  
Jérémie Nsengimana ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Growth ◽  
Cell Cycle Progression ◽  
Orphan Receptor ◽  
Cell Cycle Regulators ◽  
Loss Of Function ◽  
Proliferation Markers ◽  
Cycle Progression ◽  
Primary Tumors

Abstract Background Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma. Methods Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma. Proliferation assays, flow cytometry, and western blotting were used to evaluate cell proliferation and changes in expression levels of cell-cycle and proliferation markers. The role of ROR2 in tumor growth was assessed in xenotransplantation experiments followed by immunohistochemistry analysis of the tumors. The role of ROR2 in melanoma patients was assessed by analysis of clinical data from the Leeds Melanoma Cohort. Results Unlike previous findings describing ROR2 as an oncogene in melanoma, we describe that ROR2 prevents tumor growth by inhibiting cell-cycle progression and the proliferation of melanoma cells. The effect of ROR2 is mediated by inhibition of Akt phosphorylation and activity which, in turn, regulates the expression, phosphorylation, and localization of major cell-cycle regulators including cyclins (A, B, D, and E), CDK1, CDK4, RB, p21, and p27. Xenotransplantation experiments demonstrated that ROR2 also reduces proliferation in vivo, resulting in inhibition of tumor growth. In agreement with these findings, a higher ROR2 level favors thin and non-ulcerated primary melanomas with reduced mitotic rate and better prognosis. Conclusion We conclude that the expression of ROR2 slows down the growth of primary tumors and contributes to prolonging melanoma survival. Our results demonstrate that ROR2 has a far more complex role than originally described.

scholarly journals Regulation of Cell Division in Bacteria by Monitoring Genome Integrity and DNA Replication Status

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Peter E. Burby ◽  
Lyle A. Simmons
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Sos Response ◽  
Bacterial Cells ◽  
Cycle Progression ◽  
Content Type

ABSTRACT All organisms regulate cell cycle progression by coordinating cell division with DNA replication status. In eukaryotes, DNA damage or problems with replication fork progression induce the DNA damage response (DDR), causing cyclin-dependent kinases to remain active, preventing further cell cycle progression until replication and repair are complete. In bacteria, cell division is coordinated with chromosome segregation, preventing cell division ring formation over the nucleoid in a process termed nucleoid occlusion. In addition to nucleoid occlusion, bacteria induce the SOS response after replication forks encounter DNA damage or impediments that slow or block their progression. During SOS induction, Escherichia coli expresses a cytoplasmic protein, SulA, that inhibits cell division by directly binding FtsZ. After the SOS response is turned off, SulA is degraded by Lon protease, allowing for cell division to resume. Recently, it has become clear that SulA is restricted to bacteria closely related to E. coli and that most bacteria enforce the DNA damage checkpoint by expressing a small integral membrane protein. Resumption of cell division is then mediated by membrane-bound proteases that cleave the cell division inhibitor. Further, many bacterial cells have mechanisms to inhibit cell division that are regulated independently from the canonical LexA-mediated SOS response. In this review, we discuss several pathways used by bacteria to prevent cell division from occurring when genome instability is detected or before the chromosome has been fully replicated and segregated.

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