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Nasim Shama - - 2011
Melampomagnolide B has been identified as a new antileukemic sesquiterpene. A biotin-conjugated derivative of melampomagnolide B was designed and synthesized in order to elucidate its mechanism of action. A study of the biochemical interactions of the biotin probe suggests that melampomagnolide B derives its remarkable selectivity for leukemic cells over ...
Rushworth Stuart A - - 2011
Proteasome inhibitors such as bortezomib exhibit clinical efficacy in multiple myeloma but studies in acute myeloid leukemia (AML) have been disappointing to date. The apparent failure in AML likely reflects a lack of biological understanding that might clarify applications of proteosome inhibitors in this disease. Here we show that AML ...
Wojtysiak Dorota - - 2011
The study was performed to determine the structure and steroidogenic activity of granulosa cells derived from the germinal disc region, proximal region and distal region of the largest preovulatory ovarian follicle (F1) of the hen. The study was carried out on 34 Hy-Line Brown egg-laying hens aged 40 weeks. Morphology ...
Niu Xiao-Fang - - 2011
It was reported recently that resveratrol could sensitize a number of cancer cells to the antitumoral effects of some conventional chemotherapy drugs. The current study was designed to investigate whether resveratrol could sensitize leukemic cells to proteasome inhibitors. Leukemic cells were treated with MG132 alone or in combination with resveratrol. ...
Qin Feng-Xian - - 2011
Nucleophosmin (NPM1) is an abundant and ubiquitously expressed phosphoprotein that is known to influence solid tumors progression. However, little is known about the role of NPM1 in leukemia. Here, we knocked down the NPM1 expression by RNA interference to investigate the role of NPM1 in leukemic cells proliferation and apoptosis. ...
Chang Ming-Jin MJ Department of Biochemistry, Tulane University, New Orleans, Louisiana, - - 2010
Chimeric oncoproteins resulting from fusion of MLL to a wide variety of partnering proteins cause biologically distinctive and clinically aggressive acute leukemias. However, the mechanism of MLL-mediated leukemic transformation is not fully understood. Dot1, the only known histone H3 lysine 79 (H3K79) methyltransferase, has been shown to interact with multiple ...
Puchi Marcia - - 2010
Recently many authors have reported that cathepsin L can be found in the nucleus of mammalian cells with important functions in cell-cycle progression. In previous research, we have demonstrated that a cysteine protease (SpH-protease) participates in male chromatin remodeling and in cell-cycle progression in sea urchins embryos. The gene that ...
Lee Jennifer J Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, - - 2010
In this and a previous issue of Molecular Cell, Oda et al. (2010), Abbas et al. (2010), and Centore et al. (2010) determined that the H4K20 histone methyltransferase PR-Set7/Set8 is posttranslationally regulated by the PCNA-dependent CRL4(Cdt2) ubiquitin ligase.
Folco H Diego HD Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, - - 2010
In this issue of Molecular Cell, Hewawasam et al. (2010) and Ranjitkar et al. (2010) identify and characterize Psh1, an E3 ubiquitin ligase that specifically targets the centromeric histone Cse4 in budding yeast and limits its misincorporation at noncentromeric regions.
Bapat Sharmila A SA National Centre for Cell Science, NCCS Complex, Pune University Campus, Pune, India. - - 2010
"Epigenetic plasticity" refers to the capability of mammalian cells to alter their differentiation status via chromatin remodeling-associated alterations in gene expression. While epigenetic plasticity has been best associated with lineage commitment of embryonic stem cells, recent studies have demonstrated chromatin remodeling even in terminally differentiated normal cells, and advanced-stage melanoma ...
Desiderio Stephen S Department of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21210, United - - 2010
In developing lymphocytes, V(D)J recombination is subject to tight spatial and temporal regulation. An emerging body of evidence indicates that some of these constraints, particularly with respect to locus specificity and cell cycle phase, are enforced by regulatory cues that converge directly on the RAG proteins themselves. Active chromatin is ...
Gerlitz Gabi - - 2011
Chromatin dynamics play a major role in regulating genetic processes. Now, accumulating data suggest that chromatin structure may also affect the mechanical properties of the nucleus and cell migration. Global chromatin organization appears to modulate the shape, the size and the stiffness of the nucleus. Directed-cell migration, which often requires ...
Lopes da Rosa Jessica J Department of Molecular and Cell Biology, University of California, Berkeley, California 947202, - - 2011
Accurate chromosome segregation is dependent on the centromere-specific histone H3 isoform known generally as CenH3, or as Cse4 in budding yeast. Cytological experiments have shown that Cse4 appears at extracentromeric loci in yeast cells deficient for both the CAF-1 and HIR histone H3/H4 deposition complexes, consistent with increased nondisjunction in ...
Shen Zhen - - 2010
Origin recognition complex (ORC) plays critical roles in the initiation of DNA replication and cell-cycle progression. In metazoans, ORC associates with origin DNA during G1 and with heterochromatin in postreplicated cells. However, what regulates the binding of ORC to chromatin is not understood. We have identified a highly conserved, leucine-rich ...
Das Chandra M - - 2010
Etoposide, an inhibitor of topoisomerase II, promotes DNA damage and apoptosis of cancer cells and is a component of standard therapy for neuroblastoma. Resistance to etoposide has been observed in neural tumour cells expressing lower levels of topoisomerase II. In the present study, we have examined the contribution of epigenetic ...
O'Sullivan Roderick J RJ The Salk Institute for Biological Studies, Molecular and Cellular Biology Department, La Jolla, California, - - 2010
During replicative aging of primary cells morphological transformations occur, the expression pattern is altered and chromatin changes globally. Here we show that chronic damage signals, probably caused by telomere processing, affect expression of histones and lead to their depletion. We investigated the abundance and cell cycle expression of histones and ...
Joshi M S - - 2011
the rationale of the study was to evaluate the cytological alterations especially micronucleus (MN) and other nuclear anomalies in buccal mucosa cells of chewers to understand the genotoxic and clastogenic potential of chewing mixture (containing areca nut and tobacco as main ingredients). the buccal cytome assay involves the examination of ...
Ackermann Daniel - - 2010
Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2 characterize the ...
Melcer Shai - - 2010
ESCs (embryonic stem cells), derived from the blastocyst stage embryo, are characterized by an indefinite ability for self-renewal as well as pluripotency, enabling them to differentiate into all cell types of the three germ layers. In the undifferentiated state, ESCs display a global promiscuous transcriptional programme which is restricted gradually ...
Postberg Jan - - 2010
Understanding the evolutionary origin of the nucleus and its compartmentalized architecture provides a huge but, as expected, greatly rewarding challenge in the post-genomic era. We start this chapter with a survey of current hypotheses on the evolutionary origin of the cell nucleus. Thereafter, we provide an overview of evolutionarily conserved ...
Mello Maria Luiza S - - 2011
Lysyl oxidases (LOXs) are enzymes that permit the covalent crosslinking of the component chains of collagen and elastin. These enzymes are present inside the nuclei of certain mammalian cells. Previous studies have proposed LOX binding to histone H1 in vitro, and histone H1 is known to control global chromatin compaction ...
Narayan Pritika J - - 2010
There is increasing demand for automated image analysis of cell nuclei to be fast, objective and informative. Here, we have developed a high content analysis method for quantifying histone acetylation within any given population of cells. To demonstrate the utility of this method we quantified the effect of valproic acid ...
Bergmann Olaf - - 2011
Assays to quantify myocardial renewal rely on the accurate identification of cardiomyocyte nuclei. We previously ¹⁴C birth dated human cardiomyocytes based on the nuclear localization of cTroponins T and I. A recent report by Kajstura et al. suggested that cTroponin I is only localized to the nucleus in a senescent ...
Wang Minchuan - - 2010
PtdIns5P 4-kinases IIalpha and IIbeta are cytosolic and nuclear respectively when transfected into cells, including DT40 cells [Richardson, Wang, Clarke, Patel and Irvine (2007) Cell. Signalling 19, 1309-1314]. In the present study we have genomically tagged both type II PtdIns5P 4-kinase isoforms in DT40 cells. Immunoprecipitation of either isoform from ...
Park In-Hyun - - 2010
Research on somatic cell reprogramming has progressed significantly over the past few decades, from nuclear transfer into frogs' eggs in 1952 to the derivation of human-induced pluripotent stem (iPS) cells in the present day. In this article, I review five landmark papers that have laid the foundation for current efforts ...
Marks Paul A PA Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, Cell Biology and Genetics Program, 1275 York Ave, New York, NY 10065, USA. - - 2010
Histone deacetylase (HDAC) inhibitors are being developed as a new, targeted class of anticancer drugs. This review focuses on the mechanisms of action of the HDAC inhibitors, which selectively induce cancer cell death. There are 11 zinc-dependent HDACs in humans and the biological roles of these lysine deacetylases are not ...
Blomen V A - - 2011
Even though every cell in a multicellular organism contains the same genes, the differing spatiotemporal expression of these genes determines the eventual phenotype of a cell. This means that each cell type contains a specific epigenetic program that needs to be replicated through cell divisions, along with the genome, in ...
Schmitz Michael H A MH Institute of Biochemistry, Swiss Federal Institute of Technology Zurich (ETHZ), Schafmattstrasse 18, CH-8093 Zurich, - - 2010
When vertebrate cells exit mitosis various cellular structures are re-organized to build functional interphase cells. This depends on Cdk1 (cyclin dependent kinase 1) inactivation and subsequent dephosphorylation of its substrates. Members of the protein phosphatase 1 and 2A (PP1 and PP2A) families can dephosphorylate Cdk1 substrates in biochemical extracts during ...
Turner Emma L - - 2010
The anaphase-promoting complex (APC), a large evolutionarily conserved ubiquitin ligase complex, regulates cell cycle progression through mitosis and G(1). Here, we present data suggesting that APC-dependent cell cycle progression relies on a specific set of posttranslational histone-modifying enzymes. Multiple APC subunit mutants were impaired in total and modified histone H3 ...
Lee Hyo-Sang - - 2010
The objective was to determine whether alterations of histone acetylation status in donor cells affected inter-generic SCNT (igSCNT)-cloned embryo development. Leopard cat cells were treated with trichostatin A (TSA; a histone deacetylase inhibitor) for 48 h, and then donor cells were transferred into enucleated oocytes from domestic cats. Compared to ...
Sweet Steve M M - - 2010
We employ a stable isotope strategy wherein both histones and their methylations are labeled in synchronized human cells. This allows us to differentiate between old and new methylations on pre-existing versus newly synthesized histones. The strategy is implemented on K79 methylation in an isoform-specific manner for histones H3.1, H3.2, and ...
Mackeen Mukram M MM Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, - - 2010
Post-translational modifications on histones are an important mechanism for the regulation of gene expression and are involved in all aspects of cell growth and differentiation, as well as pathological processes including neurodegeneration, autoimmunity, and cancer. A major challenge within the chromatin field is to develop methods for the quantitative analysis ...
Lee J-H - - 2010
Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a high degree of selectivity for killing cancer cells. HDACi induce acetylation of histones and nonhistone proteins, which affect gene expression, cell cycle progression, cell migration, and cell death. The mechanism of the tumor selective action of HDACi is unclear. Here, ...
Renaudineau Yves - - 2010
Autoreactive B cells are central in the pathogenesis of autoimmune diseases (AID) not only by producing autoantibodies but also by secreting cytokines and by presenting autoantigens. Changes in DNA methylation, histone modifications, and miRNA expression, the hallmarks of epigenetic failure, characterize B cells isolated from patients with AID, highlighting the ...
Richly Holger - - 2010
Epigenetic modifications, such as DNA methylation and post-translation modifications of histones, have been shown to play an important role in chromatin structure, promoter activity, and cellular reprogramming. Large protein complexes, such as Polycomb and trithorax, often harbor multiple activities which affect histone tail modification. Nevertheless, the mechanisms underlying the deposition ...
Sato Akinori - - 2010
OBJECTIVES: To investigate the combined effect of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) and the protease inhibitor ritonavir on renal cancer cells. METHODS: Renal cancer cells (769P, 786O, A498, ACHN, Caki-1) and renal proximal tubule epithelial cells were treated with SAHA (0-5 μM) with or without ritonavir ...
Martin Catherine - - 2010
Cell type and tissue architecture correlate with genome organization in higher eukaryotes, and structural nuclear landmarks are faithfully transmitted from one cell generation to the next. However, how nuclear components find their place in the nucleus after mitosis is still a matter of debate. As the major structural proteins within ...
Dai Xiangpeng - - 2010
Somatic cell nuclear transfer (SCNT) has shown tremendous potential for understanding the mechanisms of reprogramming and creating applications in the realms of agriculture, therapeutics, and regenerative medicine, although the efficiency of reprogramming is still low. Somatic nucleus reprogramming is triggered in the short time after transfer into recipient cytoplasm, and ...
Orpinell Meritxell - - 2010
All DNA-related processes rely on the degree of chromatin compaction. The highest level of chromatin condensation accompanies transition to mitosis, central for cell cycle progression. Covalent modifications of histones, mainly deacetylation, have been implicated in this transition, which also involves transcriptional repression. Here, we show that the Gcn5-containing histone acetyl ...
Zhao Fei - - 2010
Multiple myeloma is an incurable hematological malignancy. Different studies demonstrated the occurrence of genetic and epigenetic alterations in multiple myeloma. Histone lysine methylation has emerged as a central epigenetic change in the organization of eukaryotic chromatin with far-reaching implications for the regulation of cell proliferation, cell-type differentiation, gene expression, genome ...
Singhal Nishant - - 2010
Reprogramming of somatic cells achieved by combination of the four transcription factors Oct4, Sox2, Klf4, and c-Myc has very low efficiency. To increase the reprogramming efficiency and better understand the process, we sought to identify factors that mediate reprogramming with higher efficiency. We established an assay to screen nuclear fractions ...
Doucet Christine M CM Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, 92037 CA, - - 2010
In metazoa, nuclear pore complexes (NPCs) assemble from disassembled precursors into a reforming nuclear envelope (NE) at the end of mitosis and into growing intact NEs during interphase. Here, we show via RNAi-mediated knockdown that ELYS, a nucleoporin critical for the recruitment of the essential Nup107/160 complex to chromatin, is ...
Gerlitz Gabi - - 2010
Cell migration is a fundamental process that is necessary for the development and survival of multicellular organisms. Here, we show that cell migration is contingent on global condensation of the chromatin fiber. Induction of directed cell migration by the scratch-wound assay leads to decreased DNaseI sensitivity, alterations in the chromatin ...
Daher Abdourahman - - 2010
Phoenix dactylifera (date palm) is a dioecious species displaying strong dimorphism between pistillate and staminate flowers. The mechanisms involved in the development of unisexual flowers are as yet unknown. This paper describes the results of inflorescence and flower development studies using different histological and molecular cytological approaches. Nuclear integrity and ...
Marks Paul A PA Cell Biology and Genetics Program, Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. - - 2010
There are eleven zinc dependent histone deacetylases (HDAC) in humans which have histones and many non-histone substrates. The substrates of these enzymes include proteins that have a role in regulation of gene expression, cell proliferation, cell migration, cell death, immune pathways and angiogenesis. Inhibitors of HDACs (HDACi) have been developed ...
Das Chandra M - - 2010
Etoposide, an inhibitor of topoisomerase II, promotes DNA damage and apoptosis of cancer cells and is a component of standard therapy for neuroblastoma. Resistance to etoposide has been observed in neural tumour cells expressing lower levels of topoisomerase II. In the present study, we have examined the contribution of epigenetic ...
Lai Dongmei - - 2010
Human embryonic stem cells (hESCs) are usually maintained in an undifferentiated state by coculture with mitomycin C-treated mouse embryonic fibroblasts (MEFs) as feeder cells in the presence of animal sera such as fetal bovine serum (FBS). Here, we use primary human amnion epithelial cells (hAECs) as feeder cells and human ...
Zhou Lixin - - 2010
Nucleoporin 153 (Nup153), a component of the nuclear pore complex (NPC), has been implicated in the interaction of the NPC with the nuclear lamina. Here we show that depletion of Nup153 by RNAi results in alteration of the organization of the nuclear lamina and the nuclear lamin-binding protein Sun1. More ...
Yang Cao - - 2011
To better understand the mechanisms of cytotoxicity and cell death induced by HDACI PCI-24781 in bone sarcoma cells. Four bone sarcoma cell lines were treated with PCI-24781, and the cytotoxicity was investigated. Further, accumulation of acetylated histones, p21, and PARP cleavage were evaluated in PCI-24781-treated cells. The synergistic effect of ...
Egli Dieter D The Howard Hughes Medical Institute, Stowers Medical Institute, Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA. - - 2010
Nuclear transfer allows the reprogramming of somatic cells to totipotency. The cell cycle state of the donor and recipient cells, as well as their extent of differentiation, have each been cited as important determinants of reprogramming success. Here, we have used donor and recipient cells at various cell cycle and ...
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