scholarly journals A molecular marker for centriole maturation in the mammalian cell cycle.

1995 ◽  
Vol 130 (4) ◽  
pp. 919-927 ◽  
Author(s):  
B M Lange ◽  
K Gull
Keyword(s):  
Cell Cycle ◽  
Molecular Marker ◽  
Specific Cell ◽  
Cell Cycles ◽  
Functional Maturation ◽  
Ability To Act ◽  
Molecular Events ◽  
Mammalian Cell Cycle ◽  
A Cell ◽  
First Time

The centriole pair in animals shows duplication and structural maturation at specific cell cycle points. In G1, a cell has two centrioles. One of the centrioles is mature and was generated at least two cell cycles ago. The other centriole was produced in the previous cell cycle and is immature. Both centrioles then nucleate one procentriole each which subsequently elongate to full-length centrioles, usually in S or G2 phase. However, the point in the cell cycle at which maturation of the immature centriole occurs is open to question. Furthermore, the molecular events underlying this process are entirely unknown. Here, using monoclonal and polyclonal antibody approaches, we describe for the first time a molecular marker which localizes exclusively to one centriole of the centriolar pair and provides biochemical evidence that the two centrioles are different. Moreover, this 96-kD protein, which we name Cenexin (derived from the Latin, senex for "old man," and Cenexin for centriole) defines very precisely the mature centriole of a pair and is acquired by the immature centriole at the G2/M transition in prophase. Thus the acquisition of Cenexin marks the functional maturation of the centriole and may indicate a change in centriolar potential such as its ability to act as a basal body for axoneme development or as a congregating site for microtubule-organizing material.

scholarly journals Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to oesophageal adenocarcinoma

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Connor Rogerson ◽  
Samuel Ogden ◽  
Edward Britton ◽  
Yeng Ang ◽  
Andrew D Sharrocks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Prognostic Significance ◽  
Gene Expression Signature ◽  
Chromatin Accessibility ◽  
Oesophageal Adenocarcinoma ◽  
Cell Cycle Gene ◽  
Molecular Events ◽  
Common Causes ◽  
A Cell

Oesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths. Barrett’s oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the molecular events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin to directly regulate cell cycle genes specifically in OAC cells. This new KLF5 target gene programme has potential prognostic significance as high levels correlate with poorer patient survival. Thus, the repurposing of KLF5 for novel regulatory activity in OAC provides new insights into the mechanisms behind disease progression.

The NIMA-related kinase X-Nek2B is required for efficient assembly of the zygotic centrosome in Xenopus laevis

2000 ◽  
Vol 113 (11) ◽  
pp. 1973-1984 ◽  
Author(s):  
A.M. Fry ◽  
P. Descombes ◽  
C. Twomey ◽  
R. Bacchieri ◽  
E.A. Nigg
Keyword(s):  
Cell Cycle ◽  
Xenopus Laevis ◽  
Basal Body ◽  
Chromatin Condensation ◽  
Embryonic Cells ◽  
Serine Threonine Kinase ◽  
Cell Cycles ◽  
Functional Studies ◽  
Mammalian Cell Cycle ◽  
Egg Extracts

Nek2 is a mammalian cell cycle-regulated serine/threonine kinase that belongs to the family of proteins related to NIMA of Aspergillus nidulans. Functional studies in diverse species have implicated NIMA-related kinases in G(2)/M progression, chromatin condensation and centrosome regulation. To directly address the requirements for vertebrate Nek2 kinases in these cell cycle processes, we have turned to the biochemically-tractable system provided by Xenopus laevis egg extracts. Following isolation of a Xenopus homologue of Nek2, called X-Nek2B, we found that X-Nek2B abundance and activity remained constant through the first mitotic cycle implying a fundamental difference in Nek2 regulation between embryonic and somatic cell cycles. Removal of X-Nek2B from extracts did not disturb either entry into mitosis or the accompanying condensation of chromosomes providing no support for a requirement for Nek2 in these processes at least in embryonic cells. In contrast, X-Nek2B localized to centrosomes of adult Xenopus cells and was rapidly recruited to the basal body of Xenopus sperm following incubation in egg extracts. Recruitment led to phosphorylation of the X-Nek2B kinase. Most importantly, depletion of X-Nek2B from extracts significantly delayed both the assembly of microtubule asters and the recruitment of gamma-tubulin to the basal body. Hence, these studies demonstrate that X-Nek2B is required for efficient assembly of a functional zygotic centrosome and highlight the possibility of multiple roles for vertebrate Nek2 kinases in the centrosome cycle.

scholarly journals The evaluation of proliferation ability of cardiomyocytes in heart failure

2021 ◽  
Vol 271 ◽  
pp. 03064
Author(s):  
Mengzi Gao
Keyword(s):  
Heart Failure ◽  
Cell Cycle ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Clinical Syndrome ◽  
Rna Seq ◽  
Cell Cycles ◽  
A Cell ◽  
Proliferation Ability ◽  
Heat Failure

The proliferation ability of cardiomyocytes is always under a controversial situation, especially under some stress condition such as heart failure disease and external damages. Heat failure (HF) is a complex clinical syndrome that results from left ventricular myocardial dysfunction and contributes to dyspnea, fatigue and fluid retention. The proliferation ability is related to the cell cycles and lot of cell-cycle related genes are involved in the evaluation of proliferation ability of cardiomyocytes. RNA-seq is a quite common technique in evaluate the transcription expression pattern of genes in many studies. Here in our article we analyzed the existing RNA-seq dataset to evaluate the mRNA expression level of several genes which can be indicators of the activity of cell cycles. We found that the cyclin D2 which is a cell cycle activator is upregulated in dilated cardiomyopathy (DCM) disease, indicating that the proliferation ability may be higher in DCM heart. The results throw light on the proliferation research of adult cardiomyocytes.

Early determination in the C. elegans embryo: a gene, cib-1, required to specify a set of stem-cell-like blastomeres

Development ◽  
1990 ◽  
Vol 108 (1) ◽  
pp. 107-119 ◽  
Author(s):  
R. Schnabel ◽  
H. Schnabel
Keyword(s):  
Cell Cycle ◽  
Decision Making ◽  
Stem Cell ◽  
Early Embryo ◽  
Cell Cycles ◽  
C Elegans ◽  
Lethal Mutations ◽  
A Cell ◽  
Early Decision ◽  
P Cells

The early somatic blastomeres founding the tissues in the C. elegans embryo are derived in a stem-cell-like lineage from the P cells. We have isolated maternal effect lethal mutations defining the gene cib-1 in which the P cells, P1-P3, skip a cell cycle and acquire the fates of only their somatic daughters. Therefore, the cib-1 gene is required for the specification of the stem-cell-like fate of these cells. The analysis of the development of these mutants suggests that the clock controlling the cell cycles in the early embryo is directly coupled to the fate of a cell and that there must be another developmental clock that activates the determinative inventory for the early decision-making.

scholarly journals Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes.

1996 ◽  
Vol 135 (6) ◽  
pp. 1701-1713 ◽  
Author(s):  
H A Lane ◽  
E A Nigg
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Fundamental Aspect ◽  
Early Prophase ◽  
Functional Maturation ◽  
A Cell ◽  
Gamma Tubulin ◽  
Cycle Regulation ◽  
Kinetics Of

Mammalian polo-like kinase 1 (Plk1) is structurally related to the polo gene product of Drosophila melanogaster, Cdc5p of Saccharomyces cerevisiae, and plo1+ of Schizosaccharomyces pombe, a newly emerging family of serine-threonine kinases implicated in cell cycle regulation. Based on data obtained for its putative homologues in invertebrates and yeasts, human Plk1 is suspected to regulate some fundamental aspect(s) of mitosis, but no direct experimental evidence in support of this hypothesis has previously been reported. In this study, we have used a cell duplication, microinjection assay to investigate the in vivo function of Plk1 in both immortalized (HeLa) and nonimmortalized (Hs68) human cells. Injection of anti-Plk1 antibodies (Plk1+) at various stages of the cell cycle had no effect on the kinetics of DNA replication but severely impaired the ability of cells to divide. Analysis of Plk1(+)-injected, mitotically arrested HeLa cells by fluorescence microscopy revealed abnormal distributions of condensed chromatin and monoastral microtubule arrays that were nucleated from duplicated but unseparated centrosomes. Most strikingly, centrosomes in Plk1(+)-injected cells were drastically reduced in size, and the accumulation of both gamma-tubulin and MPM-2 immunoreactivity was impaired. These data indicate that Plk1 activity is necessary for the functional maturation of centrosomes in late G2/early prophase and, consequently, for the establishment of a bipolar spindle. Additional roles for Plk1 at later stages of mitosis are not excluded, although injection of Plk1+ after the completion of spindle formation did not interfere with cytokinesis. Injection of Plk1+ into nonimmortalized Hs68 cells produced qualitatively similar phenotypes, but the vast majority of the injected Hs68 cells arrested as single, mononucleated cells in G2. This latter observation hints at the existence, in nonimmortalized cells, of a centrosome-maturation checkpoint sensitive to the impairment of Plk1 function.

scholarly journals Cyclin Cln3p Links G1 Progression to Hyphal and Pseudohyphal Development in Candida albicans

2005 ◽  
Vol 4 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Catherine Bachewich ◽  
Malcolm Whiteway
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Critical Role ◽  
Growth Conditions ◽  
Yeast Cells ◽  
Independent Manner ◽  
Cell Cycles ◽  
Environmental Controls ◽  
A Cell ◽  
Synthetically Lethal

ABSTRACT G1 cyclins coordinate environmental conditions with growth and differentiation in many organisms. In the pathogen Candida albicans, differentiation of hyphae is induced by environmental cues but in a cell cycle-independent manner. Intriguingly, repressing the G1 cyclin Cln3p under yeast growth conditions caused yeast cells to arrest in G1, increase in size, and then develop into hyphae and pseudohyphae, which subsequently resumed the cell cycle. Differentiation was dependent on Efg1p, Cph1p, and Ras1p, but absence of Ras1p was also synthetically lethal with repression of CLN3. In contrast, repressing CLN3 in environment-induced hyphae did not inhibit growth or the cell cycle, suggesting that yeast and hyphal cell cycles may be regulated differently. Therefore, absence of a G1 cyclin can activate developmental pathways in C. albicans and uncouple differentiation from the normal environmental controls. The data suggest that the G1 phase of the cell cycle may therefore play a critical role in regulating hyphal and pseudohyphal development in C. albicans.

scholarly journals CONDITIONAL MUTANTS IN CHLAMYDOMONAS REINHARDTII BLOCKED IN THE VEGETATIVE CELL CYCLE

1973 ◽  
Vol 57 (3) ◽  
pp. 760-772 ◽  
Author(s):  
Stephen H. Howell ◽  
Jay A. Naliboff
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Chlamydomonas Reinhardtii ◽  
Simple Technique ◽  
Restrictive Temperature ◽  
Permissive Temperature ◽  
General Applicability ◽  
Cell Cycles ◽  
Point Analysis ◽  
A Cell

Conditional "cycle-blocked" (cb) mutants of Chlamydomonas reinhardtii have been detected and isolated. These mutants exhibit normal vegetative growth at permissive temperature but are unable to complete a cell cycle (or a specified number of cell cycles) at restrictive temperature. A simple technique has been devised to determine the cell cycle stage in each mutant when the defective gene product, which ultimately affects cell division, completes its function. This stage is called the "block point", and is determined by scoring the residual cell division in an exponentially growing population after shift to temperature restrictive conditions. In the cb mutants isolated so far, block points representing many stages throughout the cell cycle have been found. Two categories of cb mutants are described here: one set which prevents the subsequent cell division when the cell encounters the block point after a shift to restrictive temperature, and another set which permits an additional round of cell division after the block point is encountered. The general applicability of block point analysis to other cell systems is presented.

Characterization of the unusually rapid cell cycles during rat gastrulation

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 873-883 ◽  
Author(s):  
A. Mac Auley ◽  
Z. Werb ◽  
P.E. Mirkes
Keyword(s):  
Cell Cycle ◽  
Cycle Time ◽  
Mammalian Cells ◽  
Primitive Streak ◽  
Cycle Duration ◽  
Embryonic Cells ◽  
Cell Cycle Time ◽  
Cell Cycles ◽  
A Cell ◽  
Cycle Regulation

The onset of gastrulation in rodents is associated with the start of differentiation within the embryo proper and a dramatic increase in the rate of growth and proliferation. We have determined the duration of the cell cycle for mesodermal and ectodermal cells of rat embryos during gastrulation (days 8.5 to 9.5 of gestation) using a stathmokinetic analysis. These embryonic cells are the most rapidly dividing mammalian cells yet described. Most cells of the ectoderm and mesoderm had a cell cycle time of 7 to 7.5 hours, but the cells of the primitive streak divided every 3 to 3.5 hours. Total cell cycle time was reduced by shortening S and G2, as well as G1, in contrast to cells later in development, when cell cycle duration is modulated largely by varying the length of G1. In the ectoderm and mesoderm, G1 was 1.5 to 2 hours, S was 3.5 to 4 hours, and G2 was 30 to 40 minutes. G1, S and G2 were shortened even further in the cells of the primitive streak: G1 was less than 30 minutes, S was 2 to 2.75 hours, and G2 was less than 20 minutes. Thus, progress of cells through all phases of the cell cycle is extensively modified during rodent embryogenesis. Specifically, the increased growth rate during gastrulation is associated with radical changes in cell cycle structure and duration. Further, the commitment of cells to become mesoderm and endoderm by entering the primitive streak is associated with expression of a very short cell cycle during transit of the primitive streak, such that developmental decisions determining germ layer fate are reflected in differences in cell cycle regulation.

scholarly journals Rigosertib and Cholangiocarcinoma: A Cell Cycle Affair

2021 ◽  
Vol 23 (1) ◽  
pp. 213
Author(s):  
Alessio Malacrida ◽  
Guido Cavaletti ◽  
Mariarosaria Miloso
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Cyclin B ◽  
Cell Cycles ◽  
Protein Levels ◽  
M Phase ◽  
Blotting Technique ◽  
A Cell

Rigosertib is multi-kinase inhibitor that could represent an interesting therapeutic option for non-resectable patients with cholangiocarcinoma, a very aggressive hepatic cancer with limited effective treatments. The Western blotting technique was used to evaluate alterations in the expression of proteins involved in the regulation of the cell cycle of cholangiocarcinoma EGI-1 cells. Our results show an increase in EMI1 and Cyclin B protein levels after Rigosertib treatment. Moreover, the phosphorylation of CDK1 is significantly reduced by Rigosertib, while PLK1 expression increased after 24 h of treatment and decreased after 48 h. Finally, we evaluated the role of p53. Its levels increase after Rig treatment, and, as shown in the cell viability experiment with the p53 inhibitor Pifithrin, its activity is necessary for the effects of Rigosertib against the cell viability of EGI-1 cells. In conclusion, we hypothesized the mechanism of the action of Rigosertib against cholangiocarcinoma EGI-1 cells, highlighting the importance of proteins involved in the regulation of cell cycles. The CDK1-Cyclin B complex and p53 play an important role, explaining the Block in the G2/M phase of the cell cycle and the effect on cell viability

scholarly journals Novel Response to Microtubule Perturbation in Meiosis

2005 ◽  
Vol 25 (11) ◽  
pp. 4767-4781 ◽  
Author(s):  
Andreas Hochwagen ◽  
Gunnar Wrobel ◽  
Marie Cartron ◽  
Philippe Demougin ◽  
Christa Niederhauser-Wiederkehr ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Mitotic Cell ◽  
Yeast Cells ◽  
Microtubule Depolymerization ◽  
Cycle Progression ◽  
Cell Cycles ◽  
Cycle Arrest ◽  
A Cell ◽  
Surveillance Mechanism

ABSTRACT During the mitotic cell cycle, microtubule depolymerization leads to a cell cycle arrest in metaphase, due to activation of the spindle checkpoint. Here, we show that under microtubule-destabilizing conditions, such as low temperature or the presence of the spindle-depolymerizing drug benomyl, meiotic budding yeast cells arrest in G1 or G2, instead of metaphase. Cells arrest in G1 if microtubule perturbation occurs as they enter the meiotic cell cycle and in G2 if cells are already undergoing premeiotic S phase. Concomitantly, cells down-regulate genes required for cell cycle progression, meiotic differentiation, and spore formation in a highly coordinated manner. Decreased expression of these genes is likely to be responsible for halting both cell cycle progression and meiotic development. Our results point towards the existence of a novel surveillance mechanism of microtubule integrity that may be particularly important during specialized cell cycles when coordination of cell cycle progression with a developmental program is necessary.

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