Higher cerebral functions are based upon a dynamic organization of neuronal networks. To form synaptic connections and to continuously re-shape them in a process of ongoing structural adaptation, neurons must permanently withdraw from the cell cycle. In other words, synaptic plasticity can only occur on the expense of the ability ...

Dimethylfumarate (DMF) inhibits signals transmitted by Rel proteins and is used for the treatment of inflammatory skin diseases such as psoriasis, but potential effects of DMF on tumor progression have yet not been analyzed. We show that DMF reduced melanoma growth and metastasis in severe combined immunodeficient mouse models. To ...

The CDC40 (PRP17) gene of S. cerevisiae encodes a splicing factor required for multiple events in the mitotic and meiotic cell cycles, linking splicing with cell cycle control. cdc40 mutants exhibit a delayed G(1)/S transition, progress slowly through S-phase and arrest at a restrictive temperature in the G(2) phase. In ...

Human Cdc14A is an evolutionary conserved dual-specificity protein phosphatase that reverses the modifications effected by cyclin-dependent kinases and plays an important role in centrosome duplication and mitotic regulation. Few substrates of Cdc14A have been identified, some of them with homologues in yeast that, in turn, are substrates of the Saccharomyces ...

Maintenance of genomic integrity is critical for prevention of a wide variety of adverse cellular effects including apoptosis, cellular senescence, and malignant cell transformation. Under stress conditions and even during an unperturbed cell cycle, checkpoint proteins play the key role in genome maintenance by and mediating cellular response to DNA ...

The Six1 homeoprotein is an important mediator of normal development, where it is critical for the proliferation of precursor cell populations that ultimately constitute the muscle, kidney and inner ear, among other organs. Interestingly, its overexpression has been observed in numerous cancers, where it contributes to the proliferative and metastatic ...

The retinoblastoma protein (pRb) is a central regulator of the cell cycle, controlling passage through G1 phase. Moreover, pRb has also been shown to play a direct role in the differentiation of multiple tissues, including nerve and muscle. Rb null mice display embryonic lethality, although recent data have indicated that ...

During cell cycle progression, somatic cells exhibit different patterns of intracellular Ca(2+) signals during the G(0) phase, the transition from G(1) to S, and from G(2) to M. Because pluripotent embryonic stem (ES) cells progress through cell cycle without the gap phases G(1) and G(2), we aimed to determine whether ...

The anaphase-promoting complex/cyclosome (APC/C) regulates multiple stages of the cell cycle, most prominently mitosis. We describe zebrafish with mutations in two APC/C subunits, Cdc16 and Cdc26, whose phenotypes reveal a multifaceted set of defects resulting from the gradual depletion of the APC/C. First, loss of the APC/C in dividing cells ...

Spindlin1, a meiotic spindle-binding protein that is highly expressed in ovarian cancer cells, was first identified as a gene involved in gametogenesis. It appeared to be a target for cell cycle-dependent phosphorylation and was demonstrated to disturb the cell cycle. Here we report the crystal structure of human spindlin1 to ...

Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports emphasizing increased proliferation and others pointing to a role in cell cycle exit. Here ...

Calcium signaling is a central mechanism for numerous cellular functions and particularly relevant for immune cell proliferation. However, the role of calcium influx in mitotic cell cycle progression is largely unknown. We here report that proliferating rat mast cells RBL-2H3 tightly control their major store-operated calcium influx pathway, I(CRAC), during ...

A possible cell source for a bio-artificial liver is the human hepatblastoma-derived cell line HepG2 as it confers many hepatocyte functions, however, the urea cycle is not maintained resulting in the lack of ammonia detoxification via this cycle. We investigated urea cycle activity in HepG2 cells at both a molecular ...

Candida albicans, an opportunistic human pathogen, displays three modes of growth: yeast, pseudohyphae and true hyphae, all of which differ both in morphology and in aspects of cell cycle progression. In particular, in hyphal cells, polarized growth becomes uncoupled from other cell cycle events. Yeast or pseudohyphae that undergo a ...

2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SARs were elucidated with various substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at the para-position of the 5-phenyl group showed antiproliferative activity in the order of F=CH(3) > ...

Studies in cell-culture systems and in postmortem tissue from human disease have suggested a connection between cell-cycle activation and neurodegeneration. The fruit fly Drosophila melanogaster has recently emerged as a powerful model system in which to model neurodegenerative diseases. Here we review work in the fly that has begun to ...

T regulatory cell 1 (Tr1) are low proliferating peripherally induced suppressive T cells. Engaging CD3 and CD46 on human CD4+ T cells induces a Tr1-like phenotype. In this study, we report that human Tr1-like cells do not sustain proliferation over time. The weak proliferation of these cells results first from ...

DNA replication, the process of duplication of a cell's genetic content, must be carried out with great precision every time the cell divides, so that genetic information is preserved. Control mechanisms must ensure that every base of the genome is replicated within the allocated time (S-phase) and only once per ...

The cell division cycle comprises successive rounds of genome replication and segregation that are never error-free. A complex signalling network chaperones cell cycle events to ensure that cell cycle progression does not occur until any errors detected are put right. The signalling network consists of cell cycle control proteins that ...

Multiplication of Plasmodium parasites within human erythrocytes is essential to malarial disease. The cell-division cycle of this organism, however, is still poorly understood. In other eukaryotes, various techniques for (apparent) cell-cycle synchronization have been used to shed light on the mechanisms involved in cell division and its control. Thus far ...

DNA methylation is a major determinant of epigenetic inheritance. DNA methyltransferase 1 (DNMT1) is the enzyme responsible for the maintenance of DNA methylation patterns during cell division, and deregulated expression of DNMT1 leads to cellular transformation. We show herein that AU-rich element/poly(U)-binding/degradation factor 1 (AUF1)/heterogeneous nuclear ribonucleoprotein D interacts with ...

Cell cycle events have been documented to be associated with several human neurodegenerative diseases. This review focuses on two diseases--Alzheimer's disease and ataxia telangiectasia--as well as their mouse models. Cell cycle studies have shown that ectopic expression of cell cycle markers is spatially and regional correlated well with neuronal cell ...

Evidence showing the ectopic re-expression of cell cycle-related proteins in specific vulnerable neuronal populations in Alzheimer disease led us to formulate the hypothesis that neurodegeneration, like cancer, is a disease of inappropriate cell cycle control. To test this notion, we used adenoviral-mediated expression of c-myc and ras oncogenes to drive ...

The process of cell division is highly ordered and regulated. Checkpoints exist to delay progression into the next cell cycle phase only when the previous step is fully completed. The ultimate goal is to guarantee that the two daughter cells inherit a complete and faithful copy of the genome. Checkpoints ...

Although it is well established that a transient activation of the mitogen-activated protein kinases Erk and Jnk is a crucial step in most growth promoting signaling pathways, it has also been demonstrated that a prolonged activation of these kinases can induce differentiation, cell cycle arrest, and cell senescence. We recently ...

Disruption of a proper regulation of cell proliferation can ultimately cause cancer. Most human B cell malignancies are driven by chromosomal translocations or other genetic alterations which directly affect the function of critical cell cycle proteins, such as cyclins and cyclin-dependent kinases. In addition, the transformation of indolent lymphomas into ...

It is well established that axons of the adult mammalian CNS are capable of regrowing only a limited amount after injury. Astrocytes are believed to play a crucial role in the failure to regenerate, producing multiple inhibitory proteoglycans, such as chondroitin sulphate proteoglycans (CSPGs). After spinal cord injury (SCI), astrocytes ...

Cell cycle checkpoints are surveillance mechanisms that safeguard genome integrity. While the extrinsic pathways that halt the cell cycle in response to DNA damages have been well documented, the intrinsic pathways that ensure orderly progression of cell cycle events are not well understood. We demonstrate that Drosophila MEK and ERK ...

To maintain genome stability, the cell has to limit initiation of DNA replication to once per cell cycle. Loss of this control leads to DNA rereplication with repeated firing of replication origins in the same cell cycle. Rereplication generates both ssDNA and double strand breaks, as well as activation of ...

The IKK complex includes two catalytic components, IKKalpha and IKKbeta, in addition to the scaffold protein IKKgamma/NEMO. Even though IKKalpha and IKKbeta share significant sequence homology, they have distinct biological roles with IKKbeta regulates the classical pathway of NF-kappaB activation and IKKalpha regulates the alternative pathways. In addition, it has ...

A number of recent findings support the notion of mechanistic parallels between Alzheimer disease (AD) and oncogenic processes, specifically, that neurons in AD, like cancer cells, display aberrant mitotic cell cycle re-entry. However, the mechanism that drives postmitotic neurons to reenter cell cycle remains elusive. In this study, we focused ...

We searched for evidence for a contribution of stem cells in growth of the proximal S3 segments of healthy rats. According to the stem cell model, stem cells are undifferentiated and slow cycling; the bulk of cycling cells are transit amplifying, rapidly cycling cells. We show the following. 1) By ...

The threat from cancer cells is inherently linked to cell-cycle progression, and viral genomes commonly replicate, for example, within episomes or proviruses, during mitosis. We report here that human natural killer (NK) cells bound cells in mitosis and attacked pathogenic cells in mitosis more effectively than the same cells in ...

Three structurally related protein complexes, the COP9 signalosome, the proteasome lid, and the eukaryotic translation initiation factor 3, are revealing new insights into developmental processes and into cell cycle control in healthy cells and cells exposed to genotoxic stress. Newly discovered cullin-RING E3 ubiquitin ligases assembled on the CUL4 platform ...

On May 17-21, 2006 the Cold Spring Harbor Laboratory meeting on the cell cycle reunited over 350 researchers to discuss new findings in the cell cycle field. A common thread that connected numerous presentations was the regulation of the anaphase promoting complex/cyclosome (APC/C). This was also the main theme of ...

Fragrances such as eugenol (4-allyl-2-methoxyphenol) and isoeugenol (2-methoxy-4-propenylphenol), naturally found in reasonable quantities in the essential oils of different spices, are not only common causes of contact dermatitis but also known for their antiproliferative actions. Previously, we found a cell cycle arrest and an arylhydrocarbon receptor (AhR)-mediated activation of cytochromes ...

In recent years, the intracellular oxidation-reduction (redox) state has gained increasing attention as a critical mediator of cell signaling, gene expression changes and proliferation. This review discusses the evidence for a redox cycle (i.e., fluctuation in the cellular redox state) regulating the cell cycle. The presence of redox-sensitive motifs (cysteine ...

Size control is essential for all proliferating cells, and is thought to be regulated by checkpoints that couple cell size to cell cycle progression. The aberrant cell-size phenotypes caused by mutations in the retinoblastoma (RB) tumor suppressor pathway are consistent with a role in size checkpoint control, but indirect effects ...

The packaging of DNA into nucleosomes influences the accessibility of underlying regulatory information. Nucleosome occupancy and positioning are best characterized in the budding yeast Saccharomyces cerevisiae, albeit in asynchronous cell populations or on individual promoters such as PHO5 and GAL1-10. Using FAIRE (formaldehyde-assisted isolation of regulatory elements) and whole-genome microarrays, ...

Previous studies have shown that the efficiency of phagocytosis is a function of cell cycle and that phagocytosis promotes cell cycle progression. Because phagocytosis is dependent on cellular receptors we hypothesized that Fcgamma receptors (FcgammaR) and complement receptors (CR) expression varied with cell cycle. Consequently, we used centrifugal elutriation of ...

The precise coordination of cell cycle exit and cell fate specification is essential for generating the correct proportion of retinal cell types during development. The decision to exit the cell cycle is regulated by intrinsic and extrinsic cues. There is growing evidence that neurotransmitters can regulate cell proliferation and cell ...

Critical for genomic integrity, accurate DNA replication is tightly regulated by the convergence of prereplication protein complexes (pre-RCs) to "license" replicating origins on DNA in G(1) and is activated by S-phase promoting kinases that selectively target and trigger origin firing in S-phase. To present, a checkpoint mechanism monitoring pre-RC complex ...

Activation of virulence in pathogenic fungi often involves differentiation processes that need the reset of the cell cycle and induction of a new morphogenetic program. Therefore, the fungal capability to modify its cell cycle constitutes an important determinant in carrying out a successful infection. The dimorphic fungus Ustilago maydis is ...

Cell cycle analysis using flow cytometry (FC) to measure cellular DNA content is a common procedure in drug mechanism of action studies. Although this technique lends itself readily to cell lines that grow in suspension, adherent cell cultures must be resuspended in a cumbersome and potentially invasive procedure that normally ...

Cancer treatments based on the administration of medicines at different times of the day have been shown to be more efficient against malign cells and less damaging towards healthy ones. These results might be related to the recent discovery of links between the circadian clock, (controlled by the light/dark cycle ...

The cycle inhibiting factor (Cif) belongs to a family of bacterial toxins and effector proteins, the cyclomodulins, that deregulate the host cell cycle. Upon injection into HeLa cells by the enteropathogenic Escherichia coli (EPEC) type III secretion system, Cif induces a cytopathic effect characterized by the recruitment of focal adhesion ...

Temporally and spatially controlled master regulators drive the Caulobacter cell cycle by regulating the expression of >200 genes. Rapid clearance of the master regulator, CtrA, by the ClpXP protease is a critical event that enables the initiation of chromosome replication at specific times in the cell cycle. We show here ...

The evolutionary origins of periodic phenomena in biology, such as the circadian cycle, the hibernation cycle and the sleep-wake cycle, remain a mystery. We discuss the concept of temporal compartmentalization of metabolism that takes place during such cycles, and suggest that cyclic changes in a cell's metabolic state might be ...

The APC/C is an E3 ubiquitin ligase that, by targeting substrates for proteasomal degradation, plays a major role in cell cycle control. In complex with one of two WD40 activator proteins, Cdc20 or Cdh1, the APC/C is active from early mitosis through to late G1 and during this time targets ...

APC/C complex has been known to regulate cell cycle progression via its ubiquitin E3 ligase activity that targets a number of cell cycle regulators. In a recent report, it is shown that APC/C interacts with transcription co-activators, CBP and p300, via its APC5 and APC7 subunits. The authors further demonstrate ...