Cell wars: regulation of cell survival and proliferation by cell competition

During cell competition fitter cells take over the tissue at the expense of viable, but less fit, cells, which are eliminated by induction of apoptosis or senescence. This probably acts as a quality-control mechanism to eliminate suboptimal cells and safeguard organ function. Several experimental conditions have been shown to trigger cell competition, including differential levels in ribosomal activity or in signalling pathway activation between cells, although it is unclear how those differences are sensed and translated into fitness levels. Many of the pathways implicated in cell competition have been previously linked with cancer, and this has led to the hypothesis that cell competition could play a role in tumour formation. Cell competition could be co-opted by cancer cells to kill surrounding normal cells and boost their own tissue colonization. However, in some cases, cell competition could have a tumour suppressor role, as cells harbouring mutations in a subset of tumour suppressor genes are killed by wild-type cells. Originally described in developing epithelia, competitive interactions have also been observed in some stem cell niches, where they play a role in regulating stem cell selection, maintenance and tissue repopulation. Thus competitive interactions could be relevant to the maintenance of tissue fitness and have a protective role against aging.     

Cell shrinkage and monovalent cation fluxes: role in apoptosis

The loss of cell volume or cell shrinkage has been a morphological hallmark of the programmed cell death process known as apoptosis. This isotonic loss of cell volume has recently been term apoptotic volume decrease or AVD to distinguish it from inherent volume regulatory responses that occurs in cells under anisotonic conditions. Recent studies examining the intracellular signaling pathways that result in this unique cellular characteristic have determined that a fundamental movement of ions, particularly monovalent ions, underlie the AVD process and plays an important role on controlling the cell death process. An efflux of intracellular potassium was shown to be a critical aspect of the AVD process, as preventing this ion loss could protect cells from apoptosis. However, potassium plays a complex role as a loss of intracellular potassium has also been shown to be beneficial to the health of the cell. Additionally, the mechanisms that a cell employs to achieve this loss of intracellular potassium vary depending on the cell type and stimulus used to induce apoptosis, suggesting multiple ways exist to accomplish the same goal of AVD. Additionally, sodium and chloride have been shown to play a vital role during cell death in both the signaling and control of AVD in various apoptotic model systems. This review examines the relationship between this morphological change and intracellular monovalent ions during apoptosis.     

The Role of the Anaphase-Promoting Complex/Cyclosome in Plant Growth

The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that plays a major role in the progression of the eukaryotic cell cycle. This unusual protein complex targets key cell cycle regulators, such as mitotic cyclins and securins, for degradation via the 26S proteasome by ubiquitination, triggering the metaphase-to-anaphase transition and exit from mitosis. Because of its essential role in cell cycle regulation, the APC/C has been extensively studied in mammals and yeasts, but relatively less in plants. Evidence shows that, besides its well-known role in cell cycle regulation, the APC/C also has functions beyond the cell cycle. In metazoans, the APC/C has been implicated in cell differentiation, disease control, basic metabolism and neuronal survival. Recent studies also have shed light on specific functions of the APC/C during plant development. Plant APC/C subunits and activators have been reported to play a role in cellular differentiation, vascular development, shoot branching, female and male gametophyte development and embryogenesis. Here, we discuss our current understanding of the APC/C controlling plant growth.     

Mitochondrial Contributions to Cancer Cell Physiology: Redox Balance, Cell Cycle, and Drug Resistance

Alterations in the biochemistry of mitochondria have been associated with cell transformation and the acquisition of drug resistance to certain chemotherapeutic agents, suggesting that mitochondria may play a supportive role for the cancer cell phenotype. Mitochondria are multifunctional organelles that contribute to the cellular adenosine triphosphate (ATP) pool and cellular redox balance through the production of reactive oxygen intermediates (ROI). Our laboratory has focused on these mitochondrial functions in the context of cancer cell physiology to evaluate the potential role of mitochondria as controllers of tumour cell proliferation. Low concentrations of ROI have been implicated as messengers in intracellular signal transduction mechanisms; thus an imbalance of ROI production from the mitochondria may support cancer cell growth. In addition, suppression of mitochondrial ATP production can halt cell cycle progression at two energetic checkpoints, suggesting that the use of tumor-selective agents to reduce ATP production may offer a therapeutic target for cancer growth control.     

Global analysis of a bacterial cell cycle: tracking down necessary functions and their regulators.

New, post-genomic analyses are increasing the rate at which information about highly complex processes such as bacterial growth and development can be acquired. The recent use of DNA-microarray and proteomic analysis to study the differentiating bacterium Caulobacter crescentus has provided the first global view of the requirements of a bacterium as it progresses through its cell cycle. Potential regulators of cell cycle progression have been identified, and it has been suggested that proteolysis could have a global role in regulating the bacterial cell cycle.     

Cell-cell signaling and adhesion in phagocytosis and early development of Dictyostelium

Cell-cell signaling and adhesion regulate transition from the unicellular to the multicellular stage of development in the cellular slime mold Dictyostelium. Essential gene networks involved in these processes have been identified and their interplay dissected. Heterotrimeric G protein-linked signal transduction plays a key role in regulating expression of genes mediating chemotaxis or cell adhesion, as well as coordinating actin-based cell motility during phagocytosis and chemotaxis. Two classes of cell adhesion molecules, one cadherin-like and the second belonging to the IgG superfamily, contribute to the strength of adhesion in Dictyostelium aggregates. The developmental role of genes involved in motility and adhesion, and their degree of redundancy, have been re-assessed by using novel developmental assay conditions which are closer to development in nature.     

Two faces of cytochrome c

This is an outline of the history of research on cytochrome c. Cytochromes were first discovered by Charles A. MacMunn (1886) and re-discovered by David Keilin (1925) who also identified their function in cell respiration. The role of cytochrome c in the mitochondrial electron transport chain has been well established, thus pointing to a vital role of this haemoprotein in cell function. Yet, towards the end of the last century, a novel role of cytochrome c, namely as a signal molecule for the programmed cell death (apoptosis), has been described. Differences in aminoacid composition of cytochrome c have also been used as markers of biochemical evolution. The article ends with a short biographic note on David Keilin.     

MicroRNAs-126（miR-126）的生物学功能

MicroRNAs(MiRNAs)负向调控基因的表达,在细胞分化和细胞功能调节中起着重要作用,且涉及血管新生。应用克隆和测序方法,检测出miR-126在人内皮细胞高度表达。MiR-126与许多肿瘤关系密切,miR-126通过信号传导通路负向调控肿瘤细胞增殖、迁移和侵袭,并且抑制肿瘤生长延长患者存活率;相反的,在某些肿瘤中miR-126也可通过促进肿瘤细胞血管生长加速肿瘤进展,可能是未来作为相关肿瘤治疗的手段之一。本文就miR-126在生理进程和病理进程的表达及其作用进行综述。     

Autocrine signaling involved in cell volume regulation: the role of released transmitters and plasma membrane receptors

Cell volume regulation is a basic homeostatic mechanism transcendental for the normal physiology and function of cells. It is mediated principally by the activation of osmolyte transport pathways that result in net changes in solute concentration that counteract cell volume challenges in its constancy. This process has been described to be regulated by a complex assortment of intracellular signal transduction cascades. Recently, several studies have demonstrated that alterations in cell volume induce the release of a wide variety of transmitters including hormones, ATP and neurotransmitters, which have been proposed to act as extracellular signals that regulate the activation of cell volume regulatory mechanisms. In addition, changes in cell volume have also been reported to activate plasma membrane receptors (including tyrosine kinase receptors, G-protein coupled receptors and integrins) that have been demonstrated to participate in the regulatory process of cell volume. In this review, we summarize recent studies about the role of changes in cell volume in the regulation of transmitter release as well as in the activation of plasma membrane receptors and their further implications in the regulation of the signaling machinery that regulates the activation of osmolyte flux pathways. We propose that the autocrine regulation of Ca2+-dependent and tyrosine phosphorylation-dependent signaling pathways by the activation of plasma membrane receptors and swelling-induced transmitter release is necessary for the activation/regulation of osmolyte efflux pathways and cell volume recovery. Furthermore, we emphasize the importance of studying these extrinsic signals because of their significance in the understanding of the physiology of cell volume regulation and its role in cell biology in vivo, where the constraint of the extracellular space might enhance the autocrine or even paracrine signaling induced by these released transmitters.     

Monitoring of transglutaminase2 under different oxidative stress conditions

Transglutaminase 2 (TG2) is a multifunctional calcium-dependent enzyme which catalyzes the post-translational protein crosslinking with formation of intra- or inter-molecular epsilon(gamma-glutamyl)lysine bonds or polyamine incorporation. The up-regulation and activation of TG2 have been reported in a variety of physiological events, including cell differentiation, signal transduction, apoptosis, and wound healing, as well as in cell response to stress evoked by different internal and external stimuli. Here we review TG2 role in cell response to redox state imbalance both under physiological and pathological conditions, such as neurodegenerative disorders, inflammation, autoimmune diseases and cataractogenesis, in which oxidative stress plays a pathogenetic role and also accelerates disease progression. The increase in TG activity together with mitochondrial impairment and collapse of antioxidant enzymatic cell defences have been reported to be the prominent biochemical alterations becoming evident prior to neurodegeneration. Moreover, oxidative stress-induced TG2 pathway is involved in autophagy inhibition and aggresome formation, and TG2 has been suggested to function as a link between oxidative stress and inflammation by driving the decision as to whether a protein should undergo SUMO-mediated regulation or proteasomal degradation. Literature data suggest a strong association between oxidative stress and TG2 up-regulation, which in turn may result in cell survival or apoptosis, depending on cell type, kind of stressor, duration of insult, as well as TG2 intracellular localization and activity state. In particular, it may be suggested that TG2 plays a pro-survival role when the alteration of cell redox state homeostasis is not associated with intracellular calcium increase triggering TG2 transamidation activity.     

Involvement of proteases in apoptosis

Genetically programmed (apoptotic) cell death plays a key role in cell and tissue homeostasis and in pathogenesis of various diseases. However, the mechanisms involved in apoptotic cell death are poorly understood. At present, the role of proteases in key events of apoptosis is intensively studied and discussed and the involvement of various proteolytic enzymes in the induction and development of the cell death is well-recognized. Proteases of various classes participating in apoptosis have been identified as well as some substrates of these proteases whose cleavage is critical to cell viability; specific protease inhibitors which prevent the cell death have been synthesized. This review summarizes new data on proteolytic enzymes involved in apoptosis and considers the mechanisms of activation of proteases upon induction of apoptosis and the pathways of their involvement in the cell death. The participation of nuclear proteolytic enzymes in the destabilization of chromatin structure and regulation of DNA fragmentation by endonucleases in apoptotic cells is discussed.     

Calcium signalling in bacteria

Whereas the importance of calcium as a cell regulator is well established in eukaryotes, the role of calcium in prokaryotes is still elusive. Over the past few years, there has been an increased interest in the role of calcium in bacteria. It has been demonstrated that as in eukaryotic organisms, the intracellular calcium concentration in prokaryotes is tightly regulated ranging from 100 to 300 nM. It has been found that calcium ions are involved in the maintenance of cell structure, motility, transport and cell differentiation processes such as sporulation, heterocyst formation and fruiting body development. In addition, a number of calcium-binding proteins have been isolated in several prokaryotic organisms. The characterization of these proteins and the identification of other factors suggest the possibility that calcium signal transduction exists in bacteria. This review presents recent developments of calcium in bacteria as it relates to signal transduction.     

ICE, neuronal apoptosis and neurodegeneration

Significant progress has recently occurred in the understanding of the molecular mechanisms mediating vertebrate programmed cell death, or apoptosis. New advances in this field have stemmed from the identification of ICE (caspase-1) as the founding member of the mammalian caspase cell death family. Apoptotic cell death plays an important role in neuronal cell death. Both in vitro and in vivo evidence implicates ICE as an important factor in neuronal apoptosis, especially under pathological conditions. In addition, other caspases, such as caspase-3, have also been shown to be activated and may play a role in pathological neuronal loss. Understanding the basic mechanisms mediating cell death in neurodegenerative disease may lead to the development of novel approaches for the treatment of diseases featuring apoptosis.     

Molecular mechanisms of copper homeostasis.

Copper is an essential trace element which plays a pivotal role in cell physiology as it constitutes a core part of important cuproenzymes. Novel components of copper homeostasis in humans have been identified recently which have been characterised at the molecular level. These include copper-transporting P-type ATPases, Menkes and Wilson proteins, and copper chaperones. These findings have paved the way towards better understanding of the role of copper deficiency or copper toxicity in physiological and pathological conditions.     

Caspase-dependent apoptotic pathways in CNS injury

Recent studies have suggested a role for neuronal apoptosis in cell loss following acute CNS injury as well as in chronic neurodegeneration. Caspases are a family of cysteine requiring aspartate proteases with sequence similarity to Ced-3 protein of Caenorhabditis elegans. These proteases have been found to contribute significantly to the morphological and biochemical manifestations of apoptotic cell death. Caspases are translated as inactive zymogens and become active after specific cleavage. Of the 14 identified caspases, caspase-3 appears to be the major effector of neuronal apoptosis induced by a variety of stimuli. A role for caspase-3 in injury-induced neuronal cell death has been established using semispecific peptide caspase inhibitors. This article reviews the current literature relating to pathways regulating caspase activation in apoptosis associated with acute and chronic neurodegeneration, and suggests that identification of critical upstream caspase regulatory mechanisms may permit more effective treatment of such disorders.     

SecA protein: Autoregulated initiator of secretory precursor protein translocation across theE. coli plasma membrane

Several classes ofsecA mutants have been isolated which reveal the essential role of this gene product forE. coli cell envelope protein secretion. SecA-dependent,in vitro protein translocation systems have been utilized to show that SecA is an essential, plasma membrane-associated, protein translocation factor, and that SecA's ATPase activity appears to play an essential but as yet undefined role in this process. Cell fractionation studies suggested that SecA protein is in a dynamic state within the cell, occurring in soluble, peripheral, and integral membraneous states. These data have been used to argue that SecA is likely to promote the initial insertion of secretory precursor proteins into the plasma membrane in a manner dependent on ATP hydrolysis. The protein secretion capability of the cell has been shown to translationally regulatesecA expression with SecA protein serving as an autogenous repressor, although the exact mechanism and purpose of this regulation need to be defined further.     

Drosophila neuroblast asymmetric cell division: recent advances and implications for stem cell biology

Asymmetric cell division is an evolutionarily conserved mechanism widely used to generate cellular diversity during development. Drosophila neuroblasts have been a useful model system for studying the molecular mechanisms of asymmetric cell division. In this minireview, we focus on recent progress in understanding the role of heterotrimeric G proteins and their regulators in asymmetric spindle geometry, as well as the role of an Inscuteable-independent microtubule pathway in asymmetric localization of proteins in neuroblasts. We also discuss issues of progenitor proliferation and differentiation associated with asymmetric cell division and their broader implications for stem cell biology.