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At least 127 records · Page 7Linked to original sources
PubMed1990

Phorbol ester mimics ACTH action in corticoadrenal cells stimulating steroidogenesis, blocking cell cycle, changing cell shape, and inducing c-fos proto-oncogene expression.

Cells of the Y-1 corticoadrenal line are: (a) functional, (b) cell cycle-arrested by adrenocorticotropic hormone (ACTH), (c) tumorigenic, and (d) c-Ki-ras overexpressing. We here report that the phorbol ester phorbol 12-myristate 13-acetate (PMA) mimics all ACTH-specific effects in Y-1 cells, namely: (a) steroid-ogenesis stimulation, (b) cell cycle block, and (c) cell shape change. In addition, both ACTH and PMA caused a rapid and transient induction of the c-fos proto-oncogene while having no effect on c-Ki-ras mRNA steady state levels. Dibutyryl cAMP, known to elicit ACTH effects in Y-1 cells, was a poor inducer of the c-fos gene. PMA pretreatment rendered Y-1 cells unresponsive to ACTH. These results suggest that protein kinase C is likely to be involved in the mechanisms of action of ACTH.

Adrenal Cortex Neoplasms↗
PubMed1985

Epidermal Langerhans cells--a cycling cell population.

The limited number of Langerhans cells (LC) in human epidermis and the resultant technical difficulties have left open the question of LC kinetics. In the present study using flow cytometry (FCM) we have applied 3 methods to estimate LC-DNA distribution: (1) FCM-DNA measurement on highly enriched LC suspensions, (2) FCM-correlated analysis of DNA and OKT-6(+) cells in total epidermal cell suspensions, (3) LC-enriched suspensions (70-90%) were FACS (fluorescence-activated cell sorter) sorted on microscopic slides, and stained with the Feulgen technique, and DNA was measured densitometrically. In the latter method, contaminating keratinocytes were counterlabeled with antikeratin serum to eliminate them from LC-DNA estimation. All 3 in vitro analyses clearly showed that human LC are a cycling cell population in the epidermis. The number of LC in S (1.3-3.3%) and G2/M (1.0-2.5%) phase compares with those found for keratinocytes. Assuming that this percentage of keratinocytes in S and G2/M phases is sufficient to maintain the structural integrity of the epidermis, it was suggested that LC may represent a stable, self-reproducing cell population in normal epidermis.

Cell Count↗
PubMed2005

Ckap2 regulates aneuploidy, cell cycling, and cell death in a p53-dependent manner.

We used DNA microarray screening to identify Ckap2 (cytoskeleton associated protein 2) as a novel p53 target gene in a mouse erythroleukemia cell line. DNA damage induces human and mouse CKAP2 expression in a p53-dependent manner and p53 activates the Ckap2 promoter. Overexpressed Ckap2 colocalizes with and stabilizes microtubules. In p53-null cells, overexpression of Ckap2 induces tetraploidy with aberrant centrosome numbers, suggesting disturbed mitosis and cytokinesis. In p53-competent cells, Ckap2 does not induce tetraploidy but activates p53-mediated cell cycle arrest and apoptosis. Our data suggest the existence of a functional positive feedback loop in which Ckap2 activates the G1 tetraploidy checkpoint and prevents aneuploidy.

Aneuploidy↗
PubMed1995

Evolution of the cell cycle.

Cell proliferation involves duplication of all cell constituents and their more-or-less equal segregation to daughter cells. It seems probable that the performance of primitive cell-like structures would have been dogged by poor duplication and segregation fidelity, and by parasitism. This favoured evolution of the genome and with it the distinction between 'genomic' components like chromosomes whose synthesis is periodic and most other 'functional' components whose synthesis is continuous. Eukaryotic cells evolved from bacterial ancestors whose fused genome was replicated from a single origin and whose means of segregating sister chromatids depended on fixing their identity at replication. Evolution of an endo- or cytoskeleton, initially as means of consuming other bacteria, eventually enabled evolution of the mitotic spindle and a new means of segregating sister chromatids whose replication could be initiated from multiple origins. In this primitive eukaryotic cell, S and M phases might have been triggered by activation of a single cyclin-dependent kinase whose destruction along with that of other proteins would have triggered anaphase. Mitotic non-disjunction would have greatly facilitated genomic expansion, now possible due to multiple origins, and thereby accelerated the tempo of evolution when permitted by environmental conditions.

Archaea↗
PubMed1997

Conserved and novel regulators of the plant cell cycle.

Cell division is highly regulated, both spatially and temporally, during plant development. Recent evidence implicates cyclin-dependent kinases (cdks) and their associated proteins as the principal temporal regulators of cell division. It is now known that plants contain an extended family of cdks, some of which appear to be unique to this group. Positive rate-limiting regulators of cell proliferation and growth include mitotic or B-type cyclins whose transcription is restricted to the G2 and M phases. Current research suggests that MYB-related transcription factors may be responsible for this restriction. Cdk-interacting proteins, such as cdk inhibitors and suc1 homologues, have been isolated using yeast two-hybrid approaches.

Amino Acid Sequence↗
PubMed1991

Beta 1-4-galactosyltransferase gene expression is regulated during entry into the cell cycle and during the cell cycle.

Mammalian glycosyltransferases have been implicated in a wide variety of functions besides N-linked glycosylation, including developmental processes. For this reason, we studied the effects of cell cycle and entry into the cell cycle on beta 1-4-galactosyltransferase gene expression. In this study we report that beta 1-4-galactosyltransferase (GalTase) gene expression is, indeed, regulated during the normal cell cycle, peaking during late G1-, S, and early G2 phase of the cell cycle. In addition, GalTase gene expression is regulated in a manner that resembles other "early response" genes such as jun and fos upon reentry into the cell cycle from quiescence. Finally, we show that the GalTase gene is differentially expressed during murine embryogenesis and in terminally differentiated adult tissues. It is most abundant in testis, followed by skeletal muscle and spleen. The reasons for this pattern of differential expression in adult tissues are unknown. These studies should provide important new information regarding GalTase gene expression, its regulation, and its potential link to other developmental functions.

Animals↗
PubMed1995

CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells.

Transcriptional activation of the budding yeast CLN1 and CLN2 genes during the late G1 phase of the cell cycle has been attributed to a positive feedback loop, wherein the transcription of both genes is stimulated by the accumulation of their protein products. We demonstrate that in cycling cells CLN2 does not play a role in determining the timing of its own transcriptional activation. First, we show that CLN3 alone is sufficient to maximally activate CLN2 transcription. Cells that lack functional CLN1 and CLN2 genes activate the CLN2 promoter with the same kinetics and at the same size as cells in which all three CLN genes are functional. In addition, CLN2 transcription is activated with similar kinetics in cells that have CLN2 as their only functional CLN gene and in CLN-deficient cells. Promoter analysis shows that CLN3-dependent activation of CLN2 transcription is directed primarily through the previously identified UAS1 region although another cis-acting region, UAS2, also can contribute to CLN2 activation under some conditions. The ability to activate transcription of CLN2 is not a unique property of CLN3 because ectopically expressed CLN2 can both activate the endogenous CLN2 promoter and induce Start. We propose that failure of the endogenous CLN2 gene to contribute significantly to activation of its own transcription results from its relative effectiveness at inducing Start, cell cycle progression and, subsequently, inactivation of CLN2 expression.

Base Sequence↗
PubMed1996

[The effect of an injection of N-methylformamide into mice on the cell cycle and cell morphology of ascitic hepatoma 22A].

A cell differentiating agent N-methylformamide (MF) was studied for its antitumor activity against a murine ascitic hepatoma 22A. After a 48 hour NMF administration (i/p) the tumor cell number was monitored; the distribution of these cells in the cell cycle was registered by flow cytometry, ultrastructural changes were studied by electron microscope. The polar solvent MF inhibited tumor growth, reduced mitotic activity, and nuclear/cytoplasmic ratio, led to structural complication of endoplasmic reticulum and mitochondria. The analysis of these events is suggestive that in consequence of MF effect on tumor cells, proportion of G0/G1 and M cells was decreased, while the proportion of S and G2 cells was increased.

Animals↗
PubMed2000

Expression of genes involved with cell cycle control, cell growth and chromatin modification are altered in hepatoblastomas.

Hepatoblastoma is a rare pediatric liver tumor. While much progress has been made in the treatment of the disease, very little is known about the moleculer events underlying the pathogenesis of this disease. We sought to investigate a series of hepatoblastomas for alterations in gene expression patterns with emphasis on important cell regulatory genes, including chromatin modifying enzymes, cyclin dependent kinase inhibitors, growth factors, oncogenes and cell cycle regulators. Total RNA was extracted from a series of sporadic hepatoblastomas with matched normal liver, some unmatched tumors and fetal livers, and gene expression was measured for various genes using RNase Protection Analysis (RPA). The results of this analysis show that the expression of many important regulatory genes are distinctly altered in these tumors, and a subset of tumors can be distinguished on the basis of these gene expression differences and histopathological features. Because the molecular events underlying the pathogenesis of this rare tumor are so poorly understood, this study represents a first step in determining some of the possible mechanisms involved which may provide future avenues of research.

Case-Control Studies↗
PubMed1982

Expression of theta antigen on mouse thymocytes during the cell cycle.

Cells from normal mouse thymus were subdivided according to size and analysed for surface antigen expression, protein content and DNA expression and content. It could be shown, that the expression of theta-antigen followed protein accumulation in individual cells. Protein content on the other hand, was correlated with DNA synthesis even if it varied over a greater range. Only one subgroup of small non-DNA-synthesizing cells was calculated to have a higher density indicative of a more condensed state together with an increased surface antigen content. These cells might represent the G0 state of the remnant proliferating population and most resembled the small cortical cells.

Animals↗
PubMed1991

Organelle inheritance in the yeast cell cycle.

Cell proliferation requires the inheritance of subcellular organelles, yet little is known of the molecular basis of this essential process. Recent microscopy studies of the yeast Saccharomyces cerevisiae have characterized the cellular distribution of mitochondria, vacuoles and elements of the endoplasmic reticulum and Golgi complex. In addition, genetic and microscopical approaches have allowed the isolation and analysis of mutants defective in the inheritance of mitochondria and vacuoles. These investigations are leading to the identification of molecular components mediating the movement of organelles into daughter cells and have revealed that the inheritance of organelles is coordinated with other events of the cell division cycle.

Journal Article↗
PubMed2000

Efficient lentiviral transduction of liver requires cell cycling in vivo.

Human-immunodeficiency-virus (HIV)-based lentiviral vectors are a promising tool for in vivo gene therapy. Unlike Moloney-murine-leukaemia-based retroviruses (MLV), lentiviruses are believed to stably transduce quiescent (non-cycling) cells in various organs. No previous studies, however, have directly established the cell-cycle status of any transduced cell type at the time of vector administration in vivo. In vitro studies using wild-type HIV or HIV-based vectors have shown that, in some cases, cell-cycle activation is required for infection, even though cellular mitosis is not an absolute requirement for integration. Even if the block in reverse transcription is overcome in quiescent T cells, productive infection by HIV cannot be rescued in the absence of cell-cycle activation. The potential use of these vectors for gene therapy prompted our study, which establishes a cell-cycle requirement for efficient transduction of hepatocytes in vivo.

Animals↗
PubMed2006

Cell cycle dependent apoptosis and cell cycle blocks induced by hyperthermia in HL-60 cells.

The effects of heat are strongly dependent on the time of heating at a given temperature. The relationship between treatment time and temperature for a biological isoeffect (the Arrhenius plot) has been confirmed for a variety of normal tissues and tumours. A marked change of slope occurs somewhere between 42-43 degrees C. Above this transition temperature the slope is constant for a variety of cells and tissues. Therefore, when defining thermal doses in hyperthermia studies, both the time and temperature of heating are equally important determinants. In this study, cell cycle progression and apoptosis were analysed in HL-60 cells after heating from 5-60 min at 45.0 degrees C and also heating with five different iso-dose time-temperature heat treatments. A heat shock of 5-15 min at 45.0 degrees C caused the accumulation of cells in G1 and G2/M phases after 12 h at 37 degrees C, whereas a heat shock of 20-60 min at 45.0 degrees C reduced the number of non-apoptotic cells in all phases because the number of apoptotic cells increased. The fraction of apoptotic cells followed a sigmoid curve as the heating time increased from 5-60 min at 45.0 degrees C. Cell cycle analysis showed that apoptosis occurred predominantly in S-phase cells for shorter heating times but in all phases at longer times. An isodose heat shock lower than 44.0 degrees C (42.0-43.0 degrees C) gave the same apoptotic index, while heat shock from 44.0-46.0 degrees C caused a greater than expected apoptotic index. Thus, there was a transition at 44.0 degrees C in HL-60 cells, above which apoptosis increased rapidly. These results indicate that isodose analysis based on clonogenic survival in fibroblast cells may not be relevant for cell types which readily undergo apoptosis. Clonogenic survival was also compared with apoptosis for HL-60 cells and an apoptotic-resistant derivative cell line, HWC-2, heated for various times at 45.0 degrees C. Survival based on a clonogenic assay was much lower than survival based only on apoptotic index at all times for HL-60 cells. HWC-2 cells did not undergo apoptosis and also had a higher clonogenic survival than HL-60 cells.

Apoptosis↗
PubMed1999

Cellular ras and cyclin D1 are required during different cell cycle periods in cycling NIH 3T3 cells.

Novel techniques were used to determine when in the cell cycle of proliferating NIH 3T3 cells cellular Ras and cyclin D1 are required. For comparison, in quiescent cells, all four of the inhibitors of cell cycle progression tested (anti-Ras, anti-cyclin D1, serum removal, and cycloheximide) became ineffective at essentially the same point in G1 phase, approximately 4 h prior to the beginning of DNA synthesis. To extend these studies to cycling cells, a time-lapse approach was used to determine the approximate cell cycle position of individual cells in an asynchronous culture at the time of inhibitor treatment and then to determine the effects of the inhibitor upon recipient cells. With this approach, anti-Ras antibody efficiently inhibited entry into S phase only when introduced into cells prior to the preceding mitosis, several hours before the beginning of S phase. Anti-cyclin D1, on the other hand, was an efficient inhibitor when introduced up until just before the initiation of DNA synthesis. Cycloheximide treatment, like anti-cyclin D1 microinjection, was inhibitory throughout G1 phase (which lasts a total of 4 to 5 h in these cells). Finally, serum removal blocked entry into S phase only during the first hour following mitosis. Kinetic analysis and a novel dual-labeling technique were used to confirm the differences in cell cycle requirements for Ras, cyclin D1, and cycloheximide. These studies demonstrate a fundamental difference in mitogenic signal transduction between quiescent and cycling NIH 3T3 cells and reveal a sequence of signaling events required for cell cycle progression in proliferating NIH 3T3 cells.

3T3 Cells↗
PubMed1997

The Drosophila gene morula inhibits mitotic functions in the endo cell cycle and the mitotic cell cycle.

In the endo cell cycle, rounds of DNA replication occur in the absence of mitosis, giving rise to polyploid or polytene cells. We show that the Drosophila morula gene is essential to maintain the absence of mitosis during the endo cycle. During oogenesis in wild-type Drosophila, nurse cells become polyploid and do not contain cyclin B protein. Nurse cells in female-sterile alleles of morula begin to become polyploid but revert to a mitotic-like state, condensing the chromosomes and forming spindles. In strong, larval lethal alleles of morula, the polytene ring gland cells also inappropriately regress into mitosis and form spindles. In addition to its role in the endo cycle, morula function is necessary for dividing cells to exit mitosis. Embryonic S-M cycles and the archetypal (G1-S-G2-M) cell cycle are both arrested in metaphase in different morula mutants. These phenotypes suggest that morula acts to block mitosis-promoting activity in both the endo cycle and at the metaphase/anaphase transition of the mitotic cycle. Consistent with this, we found cyclin B protein to be inappropriately present in morula mutant nurse cells. Thus morula serves a dual function as a cell cycle regulator that promotes exit from mitosis and maintains the absence of mitosis during the endo cycle, possibly by activating the cyclin destruction machinery.

Alleles↗
PubMed2001

Cell cycle analysis and expression of cell cycle regulator genes in myeloma cells overexpressing cyclin D1.

Among the recently discovered myeloma-specific gene alterations associated with chromosomal translocations, cyclin D1/PRAD1/Bcl-1 overexpression caused by t(11;14)(q13;q32) is considered to be the most frequent in myeloma patients and cell lines, and may be a prognostic factor clinically. To elucidate the cellular biological role of overexpressed cyclin D1 in myeloma cells, we examined the mRNA expression levels of cell cycle regulators including three cyclin Ds, cyclin-dependent kinase inhibitors (CDK-Is) and accelerators. Cyclin D1 overexpression was clearly demonstrated in the lines with abnormal 11q13 and associated with overexpression of S and G2 accelerator genes. The cyclin D1-overexpressing lines tended to have a shortened G1 phase compared with the non-expressing lines. In addition, artificial silencing using antisense oligonucleotides for cyclin D1 suppressed the growth rate of some but not all cyclin D1-overexpressing cells. These results indicate that overexpression of cyclin D1 caused by cytogenetic abnormalities may make cells progress through the cell cycle rapidly, but it seems that other factors such as cyclin D2 and translocation-related genes affect the cell cycle progression in myeloma cells.

Cell Cycle↗
PubMed2004

GW182 is critical for the stability of GW bodies expressed during the cell cycle and cell proliferation.

A novel cytoplasmic compartment referred to as GW bodies was initially identified using human autoantibodies to a 182 kDa protein named GW182. GW bodies are small, generally spherical, cytoplasmic domains that vary in number and size in several mammalian cell types examined to date. Based on our earlier studies, GW bodies were proposed to be cytoplasmic sites for mRNA storage and/or degradation. In the present study, immunogold electron microscopy identified electron dense structures of 100-300 nm diameter devoid of a lipid bilayer membrane. These structures appeared to comprise clusters of electron dense strands of 8-10 nm in diameter. By costaining with CENP-F and PCNA, and employing a double-thymidine block to synchronize HeLa cells, GW bodies were observed to be small in early S phase and larger during late S and G2 phases of the cell cycle. The majority of GW bodies disassembled prior to mitosis and small GW bodies reassembled in early G1. The analysis of GW bodies in two experimental models of cell proliferation using reversal of 3T3/serum-starvation and concanavalin A stimulation of mouse splenocytes and T cells, revealed that proliferating cells contained larger, brighter, and more numerous GW bodies as well as up to a fivefold more total GW182 protein than quiescent cells. In vitro gene knockdown of GW182 led to the disappearance of GW bodies demonstrating that GW182 is a critical component of GW bodies. The incremental expression of the GW182 protein in cells induced to proliferate and the cyclic formation and breakdown of GW bodies during mitosis are intriguing in view of the notion that GW bodies are specialized centers involved in maintaining stability and/or controlling degradation of mRNA.

3T3 Cells↗