FoxO transcription factors are an evolutionary conserved subfamily of the forkhead transcription factors, characterized by the forkhead DNA-binding domain. FoxO factors regulate a number of cellular processes involved in cell-fate decisions in a cell-type- and environment-specific manner, including metabolism, differentiation, apoptosis and proliferation. A key mechanism by which FoxO determines ...

The control of growth of lymphocyte populations is crucial to the physiological regulation of the immune system, and to the prevention of both leukaemic and autoimmune disease. This control is mediated through modulation of the cell cycle and regulation of cell death. During log-phase growth the rate of proliferation is ...

Proliferating cell nuclear antigen (PCNA) is a homotrimeric ring-shaped protein that encircles the DNA and acts as a stationary loading platform for multiple, transiently interacting partners participating in various DNA transactions. This essential cellular component, originally characterized as a nuclear antigen of dividing cells, is evolutionary highly conserved from yeast ...

When cell cycle studies are performed following cell cycle synchronization, it is possible that critical properties of an actively cycling cell will be overlooked. For this reason past studies have not revealed critical aspects of cell cycle control; such as how a cell determines when to exit the cell cycle, ...

Macrophage immigration inhibitory factor (MIF) is a ubiquitously expressed proinflammatory mediator that has also been implicated in cell growth, cell cycle and carcinogenesis. In this study, we demonstrate siRNA-mediated knockdown of MIF results in G(0)/G(1) cell cycle arrest in HEK293 cells. To elucidate the molecular mechanism of cell cycle perturbation ...

DNA damage response recruits complex molecular machinery involved in DNA repair, arrest of cell cycle progression, and potentially in activation of apoptotic pathway. Among the first responders is the Mre11- (MRN) complex of proteins (Mre11, Rad50, Nbs1), essential for activation of ATM; the latter activates checkpoint kinase 2 (Chk2) and ...

Reversible protein ubiquitination is a crucial mechanism regulating the progression through the eukaryotic cell cycle. Ubiquitin-dependent signaling is terminated by specific deubiquitinating enzymes (DUBs), which now are known to be integral components of the core cell cycle machinery and cell cycle checkpoints. The importance of DUBs for cell cycle control ...

Ordered progression through the cell cycle is essential to maintain genomic stability, and fundamental to this is ubiquitin-mediated proteolysis. In particular, the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase destabilises specific regulators at defined times in the cycle to ensure that each round of DNA replication is followed by cell division. Thus, ...

Cell cycle lengths vary widely among different cells within an animal, yet mechanisms of cell cycle length regulation are poorly understood. In the Caenorhabditis elegans embryo, the first cell division produces two cells with different cell cycle lengths, which are dependent on the conserved partitioning-defective (PAR) polarity proteins. We show ...

The retinoblastoma (RB) protein is a eukaryotic tumor suppressor and negative cell-cycle regulator. Chlamydomonas reinhardtii cells that lack the RB homolog MAT3 show loss of size checkpoint control and deregulated cell-cycle progression leading to the production of tiny cells. We carried out an insertional mutagenesis screen to isolate bypass suppressors ...

Abstract Background Vinca alkaloids are an important class of anticancer agents and semisynthetic vinca alkaloids are developed to improve the therapeutic index of this class of drugs. In the present study, a direct comparison was made between vinflunine and vinorelbine regarding their radiosensitising and cell cycle effects. Methods Four human ...

In a no-wait robotic cell, we proved that the smallest degree of an optimal cycle, kappa, can take any value between 1 and (m+1)/2. We also proved that kappa can be equal to m-1 for m=4 and that there exists instances for which kappa greater or equal to m-1 for ...

Previous studies have revealed many parallels in the cell cycle regulation of the Ace2 and Swi5 transcription factors. Although both proteins begin entry into the nucleus near the start of mitosis, here we show that Ace2 accumulates in the nucleus and binds DNA about 10 min later in the cell ...

The c-myc proto-oncogene is rapidly activated by serum and regulates genes involved in metabolism and cell cycle progression. This gene is thereby uniquely poised to coordinate both the metabolic and cell cycle regulatory events required for cell cycle entry. However, this function of Myc has not been evaluated. Using a ...

The cell-cycle transition from G1 to S phase has been difficult to visualize. We have harnessed antiphase oscillating proteins that mark cell-cycle transitions in order to develop genetically encoded fluorescent probes for this purpose. These probes effectively label individual G1 phase nuclei red and those in S/G2/M phases green. We ...

When observing living cells, only mitosis is easily distinguishable from other phases of the cell cycle. In this issue, Sakaue-Sawano et al. (2008) present a method to visually distinguish cells at different phases of the cell cycle by the expression of colored fusion proteins that are under the control of ...

Apicomplexa are obligate intracellular pathogens that have fine-tuned their proliferative strategies to match a large variety of host cells. A critical aspect of this adaptation is a flexible cell cycle that remains poorly understood at the mechanistic level. Here we describe a forward genetic dissection of the apicomplexan cell cycle ...

The six-subunit origin recognition complex (ORC) acts as a landing pad for factors that initiate DNA replication by binding to replication origins. In addition, ORC is involved in other processes such as transcriptional gene silencing and sister chromatid cohesion in Saccharomyces cerevisiae. However, whether these functions of ORC are specific ...

Acute myeloid leukemia (AML) cells exposed to genotoxic agents arrest their cell cycle at the G2/M checkpoint and are inherently chemoresistant. To understand the mechanism of this chemoresistance, we compared the ability of immature CD34+ versus mature CD34- AML cell lines (KG1a and U937, respectively) to recover from a DNA ...

The intestinal parasite Giardia lamblia undergoes cell differentiations that entail entry into and departure from the replicative cell cycle. The pathophysiology of giardiasis depends directly upon the ability of the trophozoite form to replicate in the host upper small intestine. Thus, cell proliferation is tightly linked to disease. However, studies ...

Characterization of the transcriptional regulatory network of the normal cell cycle is essential for understanding the perturbations that lead to cancer. However, the complete set of cycling genes in primary cells has not yet been identified. Here, we report the results of genome-wide expression profiling experiments on synchronized primary human ...

Cells treated with low doses of linoleic acid hydroperoxide (LoaOOH) exhibit a cell-cycle delay that may provide a mechanism to overcome oxidative stress. Strains sensitive to LoaOOH from the genome-wide deletion collection were screened to identify deletants in which the cell-cycle delay phenotype was reduced. Forty-seven deletants were identified that ...

A prerequisite of calcium signaling is the maintenance of cytoplasmic free Ca(2+) within a narrow, sub-micromolar range, compatible with cell viability. A variety of stress inducing agents and drugs can lead to a disruption of calcium homeostasis with ensuing toxicity. Amiodarone, an anti-arrhythmic drug with broad range microbicidal effect, has ...

We have characterized a distinct, late transitional B cell subset, CD21(int) transitional 2 (T2) B cells. In contrast to early transitional B cells, CD21(int) T2 B cells exhibit augmented responses to a range of potential microenvironmental stimuli. Adoptive transfer studies demonstrate that this subset is an immediate precursor of both ...

Cell size homeostasis in proliferating cell populations is maintained in part by linking the initiation of a cell division cycle to growth such that a specific "size threshold" must be achieved prior to cell cycle initiation. In Saccharomyces cerevisiae the size threshold is responsive to environmental conditions and cell cycle ...

Cancer cells are growing without control and it is therefore important to understand the mechanisms limiting the growth of normal cells. Before a cell can divide it must make a new set of chromosomes, so that both daughter cells receive the same genetic information as their mother. The period of ...

Cell cycle control and migration are critical processes during development and maintenance of tissue functions. Recently, primary cilia were shown to take part in coordination of the signaling pathways that control these cellular processes in human health and disease. In this review, we present an overview of the function of ...

BACKGROUND: Statins, a family of 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitors, are being investigated for the therapy and prevention of cancers. Here we aimed to investigate the effects of simvastatin on chronic myelogenous leukemia (CML) cells in vitro and in vivo, and to elucidate the mechanisms. METHODS: Cell proliferation and ...

Chloroquine is an antimalarial drug that has been used in the treatment and prophylaxis of malaria since the 1950s. The present study was undertaken to examine the effects of chloroquine on Bcap-37 human breast cancer cells' growth, cell cycle modulation, apoptosis induction, and associated molecular alterations in vitro. The chloroquine ...

The re-expression of multiple cell cycle markers representing various cell cycle phases in postmitotic pyramidal neurons suggests that neurons in Alzheimer disease (AD) attempt to re-enter the cell cycle. Entry into the cell cycle requires activation of G1 to S phase cell cycle proteins, among which retinoblastoma protein (pRb) is ...

Alzheimer's disease (AD), the leading cause of senile dementia, has become a considerable social and economical problem. Current AD therapeutics provide mainly symptomatic short-term benefit, rather than targeting disease mechanisms. The hallmarks for AD are beta-amyloid plaques, neurofibrillary tangles, and regionalized neuronal loss. Additional neuropathological features have been described that ...

Rad9 is required for the activity of the genotoxin-induced checkpoint signaling pathway to control cell cycle progress and maintain genomic stability. In the fission yeast S. Pombe and chicken cells, the Rad9 gene is essential for prevention of premature chromosomal condensation (PCC:S/M checkpoint control). However, precise features in the S/M ...

Adult brains differ among species in the proportional sizes of their major subdivisions. For example, the telencephalon occupies 71% of the entire brain in parakeets (Melopsittacus undulatus) but only 54% in quail (Colinus virginianus). In contrast, the tectum is smaller in parakeets than in quail. To determine whether these differences ...

From general considerations of the basic physiological properties of the cell division cycle, we deduce what the dynamical properties of the underlying molecular control system must be. Then, taking a few hints from the biochemistry of cyclin-dependent kinases (the master regulators of the eukaryotic cell cycle), we guess what molecular ...

Cell proliferation requires nutrients, energy, and biosynthetic activity to duplicate all macromolecular components during each passage through the cell cycle. It is therefore not surprising that metabolic activities in proliferating cells are fundamentally different from those in nonproliferating cells. This review examines the idea that several core fluxes, including aerobic ...

Mixed lineage leukemia 5 (MLL5) encodes a mammalian trithorax group (TrxG) protein located within chromosome band 7q22, which is a frequently deleted region found in acute myeloid malignancies. Trithorax and polycomb (PcG) group proteins are evolutionarily conserved transcriptional regulators that maintain the expression of Homeobox (HOX) genes at the epigenetic ...

BACKGROUND: Despite continuing advances in our understanding of AIDS pathogenesis, the mechanism of CD4+ T cell depletion in HIV-1-infected individuals remains unclear. The HIV-1 Vpr accessory protein causes cell death, likely through a mechanism related to its ability to arrest cells in the G2,M phase. Recent evidence implicated the scaffold ...

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as ...

The target of rapamycin (Tor) protein plays central roles in cell growth. Rapamycin inhibits cell growth and promotes cell cycle arrest at G1 (G0). However, little is known about whether Tor is involved in other stages of the cell division cycle. Here we report that the rapamycin-sensitive Tor complex 1 ...

BACKGROUND: We investigate the cycles in the transcription network of Saccharomyces cerevisiae. Unlike a similar network of Escherichia coli, it contains many cycles. We characterize properties of these cycles and their place in the regulatory mechanism of the cell. RESULTS: Almost all cycles in the transcription network of Saccharomyces cerevisiae ...

BACKGROUND: The cell cycle has long been an important model to study the genome-wide transcriptional regulation. Although several methods have been introduced to identify cell cycle regulated genes from microarray data, they can not be directly used to investigate cell cycle regulated transcription factors (CCRTFs), because for many transcription factors ...

Increasing knowledge on the cell cycle deregulations in cancers has promoted the introduction of phytochemicals, which can either modulate signaling pathways leading to cell cycle regulation or directly alter cell cycle regulatory molecules, in cancer therapy. Most human malignancies are driven by chromosomal translocations or other genetic alterations that directly ...

BACKGROUND: Cardiomyocyte (CM) cell cycle analysis has been impeded because of a reliance on primary neonatal cultures of poorly proliferating cells or chronic transgenic animal models with innate compensatory mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We describe an in vitro model consisting of monolayer cultures of highly proliferative embryonic stem (ES) cell-derived CM. ...

BACKGROUND: Eukaryotic cell cycle is a complex process and is precisely regulated at many levels. Many genes specific to the cell cycle are regulated transcriptionally and are expressed just before they are needed. To understand the cell cycle process, it is important to identify the cell cycle transcription factors (TFs) ...

Tripeptidyl-peptidase II (TPPII) is a serine peptidase highly expressed in malignant Burkitt's lymphoma cells (BL). We have previously shown that overexpression of TPPII correlates with chromosomal instability, centrosomal and mitotic spindle abnormalities and resistance to apoptosis induced by spindle poisons. Furthermore, TPPII knockdown by RNAi was associated with endoreplication and ...

Cell cycle checkpoints are pivotal mechanisms safeguarding genome stability. Cells that harbor defects in checkpoints are predisposed to genome instability and neoplastic transformation. Two structurally-unrelated protein kinases, CHK1 and CHK2, are implicated in several major checkpoints of the cell cycle, providing a crucial linkage between the upstream sensors of the ...

The cell cycle database is a biological resource that collects the most relevant information related to genes and proteins involved in human and yeast cell cycle processes. The database, which is accessible at the web site http://www.itb.cnr.it/cellcycle, has been developed in a systems biology context, since it also stores the ...

PKC412 is a staurosporine derivative that inhibits several protein kinases including FLT3, and is highly anticipated as a novel therapeutic agent for acute myeloblastic leukemia (AML) carrying FLT3 mutations. In this study, we show that PKC412 exerts differential cell cycle effects on AML cells depending on the presence of FLT3 ...

Progression of a cell through the division cycle is tightly controlled at different steps to ensure the integrity of genome replication and partitioning to daughter cells. From published experimental evidence, we propose a molecular mechanism for control of the cell division cycle in Caulobacter crescentus. The mechanism, which is based ...

Cell cycle and circadian rhythms are conserved from cyanobacteria to humans with robust cyclic features. Recently, molecular links between these two cyclic processes have been discovered. Core clock transcription factors, Bmal1 and Clock (Clk), directly regulate Wee1 kinase, which inhibits entry into the mitosis. We investigate the effect of this ...