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    1161 results match your criteria Advances in Enzyme Regulation [Journal]

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    RAS oncogene-mediated deregulation of the transcriptome: from molecular signature to function.
    Adv Enzyme Regul 2011 20;51(1):126-36. Epub 2010 Nov 20.
    Laboratory of Molecular Tumor Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
    Transcriptome analysis of cancer cells has developed into a standard procedure to elucidate multiple features of the malignant process and to link gene expression to clinical properties. Gene expression profiling based on microarrays provides essentially correlative information and needs to be transferred to the functional level in order to understand the activity and contribution of individual genes or sets of genes as elements of the gene signature. To date, there exist significant gaps in the functional understanding of gene expression profiles. Read More

    Temporal and functional analysis of DNA replicated in early S phase.
    Adv Enzyme Regul 2011 18;51(1):257-71. Epub 2010 Nov 18.
    Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
    In summary, recently developed technologies have begun to draw back the curtain of mystery that obscures some of the basic mechanisms of DNA replication at multiple levels. Studies using extended DNA and chromatin fiber techniques have proven valuable for identifying the location of origins of replication at specific genomic sites and determining their temporal order of replication, for identifying and quantifying sites of DNA damage and localizing chromatin proteins in relation to sites of DNA replication. The future potential of these methods include further discoveries in functional genomics and contributions to the elucidation of the histone code. Read More

    Genetic ablation of S6-kinase does not prevent processing of SREBP1.
    Adv Enzyme Regul 2011 18;51(1):280-90. Epub 2010 Nov 18.
    Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, London, UK.
    The SREBP family of transcription factors regulates the expression of genes involved in fatty acid and cholesterol biosynthesis. The activation of SREBP transcription factors requires proteolytic cleavage of the inactive precursor and nuclear translocation of the mature form of the protein. It has been shown that nuclear accumulation of the mature form of SREBP1 is induced in response to activation of the serine/threonine kinase Akt, an important effector of the Ras/PI3-kinase signalling pathway. Read More

    Sphingosine kinase localization in the control of sphingolipid metabolism.
    Adv Enzyme Regul 2011 12;51(1):229-44. Epub 2010 Nov 12.
    Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
    The sphingosine kinases (sphingosine kinase-1 and -2) have been implicated in a variety of physiological functions. Discerning their mechanism of action is complicated because in addition to producing the potent lipid second messenger sphingosine-1-phosphate, sphingosine kinases, both by producing sphingosine-1-phosphate and consuming sphingosine, have profound effects on sphingolipid metabolism. Sphingosine kinase-1 translocates to the plasma membrane upon agonist stimulation and this translocation is essential for the pro-oncogenic properties of this enzyme. Read More

    Inositol and its derivatives: their evolution and functions.
    Adv Enzyme Regul 2011 9;51(1):84-90. Epub 2010 Nov 9.
    School of Biosciences, University of Birmingham, Birmingham, United Kingdom.
    Ins and Ins phospholipids are present in and are made by most Archaea and all eukaryotes. Relatively few bacteria possess Ins phospholipids: and only one major grouping, the Actinobacteria, is known to have evolved multiple functions for Ins derivatives. The Ins phospholipids of all organisms, whether they have diradylglycerol or ceramide backbones, seem to use the same Ins1P headgroup stereochemistry, so they are probably made by evolutionarily conserved pathways. Read More

    Receptor tyrosine kinase signaling--a proteomic perspective.
    Adv Enzyme Regul 2011 5;51(1):293-305. Epub 2010 Nov 5.
    Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA.
    The RTKs are one of the most important families mediating transmembrane signaling and they participate and are instrumental in regulating a broad range of physiological activities. Indeed, tyrosine kinases in general, and the processes that they control and/or stimulate, provide a rich source of drug targets, particularly in growth related disorders such as cancer (Zwick et al., 2002; Krause and Van Etten, 2005). Read More

    Control of eukaryotic gene expression: gene loops and transcriptional memory.
    Adv Enzyme Regul 2011 29;51(1):118-25. Epub 2010 Oct 29.
    Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, NJ 08854-0009, United States.
    Gene loops are dynamic structures that juxtapose promoter–terminator regions of Pol II-transcribed genes. Although first described in yeast, gene loops have now been identified in yeast and mammalian cells. Looping requires components of the transcription preinitiation complex, the pre-mRNA 30-end processing machinery, and subunits of the nuclear pore complex. Read More

    The impact of PTEN regulation by CK2 on PI3K-dependent signaling and leukemia cell survival.
    Adv Enzyme Regul 2011 28;51(1):37-49. Epub 2010 Oct 28.
    Instituto de Medicina Molecular, Faculdade de Medicina, Unversidade de Lisboa, Lisboa, Portugal.
    Gene alterations affecting elements of PI3K signaling pathway do not appear to be sufficient to explain the extremely high frequency of PI3K signaling hyperactivation in leukemia. It has been known for long that PTEN phosphorylation at the C-terminal tail, in particular by CK2, contributes to the stabilization and simultaneous inhibition of this critical tumor suppressor. However, direct evidence of the involvement of this mechanism in cancer has been gathered only recently. Read More

    Regulation and roles of PI3Kβ, a major actor in platelet signaling and functions.
    Adv Enzyme Regul 2011 28;51(1):106-16. Epub 2010 Oct 28.
    Inserm, U563, Université Toulouse III, Centre de Physiopathologie de Toulouse Purpan, CHU-Purpan, Toulouse, France.
    Phosphoinositide 3-kinases (PI3Ks) are important signaling enzymes involved in the regulation of a number of critical cell functions. Significant progress has been made during the last few years in defining the implication of individual PI3K isoforms. The role of the class IA PI3Kβ in different cell types has only been recently uncovered by the use of isoform-selective inhibitors and the development of mouse models harboring p110β catalytic subunit knock-out or germline knock-in of a kinase-dead allele of p110β. Read More

    The mechanism of contribution of integrin linked kinase (ILK) to epithelial-mesenchymal transition (EMT).
    Adv Enzyme Regul 2011 28;51(1):195-207. Epub 2010 Oct 28.
    Chair of Medical Biochemistry Jagiellonian University Medical College, Kraków, Poland.
    Integrin linked kinase (ILK) is ubiquitously expressed serine/threonine protein kinase, a binding partner of β1 and β3 integrin subunit as a cytoplasmic effector of integrin receptors that functionally links them to the actin cytoskeleton.We postulate that ILK is important enzyme involved in epithelial-mesenchymal transition (EMT) a critical event in the process of cancer progression. Commonly used EMT molecular markers include among others increased expression of N-cadherin and vimentin, nuclear localization of β-catenin, and the decrease of E-cadherin synthesis. Read More

    The signaling role of inositol hexakisphosphate kinases (IP6Ks).
    Adv Enzyme Regul 2011 28;51(1):74-82. Epub 2010 Oct 28.
    Cell Biology Unit, Medical Research Council Laboratory for Molecular Cell Biology (MRC-LMCB), University College London, London, UK.
    The past ten years have seen a contained explosion of interest in inositol pyrophosphates. The early cloning of the IP6Ks and the more recent identification of the PP-IP5Ks have allowed the development of essential experimental tools to investigate the physiological role of inositol pyrophosphates. However, for this exciting field of research to gain momentum, simpler and more reliable research protocols need to be further developed. Read More

    Deciphering the signaling pathways of cancer stem cells of glioblastoma multiforme: role of Akt/mTOR and MAPK pathways.
    Adv Enzyme Regul 2011 28;51(1):164-70. Epub 2010 Oct 28.
    Department of Neurosurgery, New York Medical College, Valhalla, NY 10595, USA.
    These findings emphasize that the mTOR pathway may contribute to maintenance of quiescence of CSCs, and provide a basis for manipulating CSCs in the treatment of GBM. Future research should focus on further defining the PI3K/Akt/mTOR molecular network in the regulation of stem cell quiescence and provide rationale for targeting the cancer-initiating cells of GBM. Read More

    Leukotriene B4 receptors: novel roles in immunological regulations.
    Adv Enzyme Regul 2011 28;51(1):59-64. Epub 2010 Oct 28.
    Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
    Mammals have at least two receptors for LTB4; high-affinity BLT1 and low-affinity BLT2, both of which are GPCRs. 12-HHT serves as a more potent and abundant ligand for BLT2 than LTB4. BLT1 is expressed in a variety of inflammatory and immune cells including granulocytes, eosinophils, macrophages, differentiated Th1, Th2 and Th17 cells, effecter CD8+ T cells, dendritic cells and osteoclasts. Read More

    Hits, Fhits and Nits: beyond enzymatic function.
    Adv Enzyme Regul 2011 28;51(1):208-17. Epub 2010 Oct 28.
    Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University Medical Center, Columbus, OH 43210, United States.
    We have briefly summarized what is known about these proteins, but in closing wish to feature the outstanding questions. Hint1 was discovered mistakenly as an inhibitor of Protein Kinase C and designated Pkci, a designation that still confuses the literature. The other Hint family members were discovered by homology to Hint1. Read More

    Regulation of B cell survival, development and function by inositol 1,4,5-trisphosphate 3-kinase B (Itpkb).
    Adv Enzyme Regul 2011 28;51(1):66-73. Epub 2010 Oct 28.
    Institut de Recherches Interdisciplinaires en Biologie Humaine et Moléculaire (IRIBHM), Faculté de Médecine, Université Libre de Bruxelles, Gosselies, Belgium.
    In mammals, Ins(1,4,5)P3, the well known calcium mobilization messenger, is phosphorylated in the cytosol at the 3-position of the inositol ring to yield Ins(1,3,4,5)P4 by Ins(1,4,5)P3 3-kinases A, B and C isoforms as well as by inositol polyphosphate multikinase (Ipmk). Studies in gene-deficient mice have revealed that these enzymes and Ins(1,3,4,5)P4, their reaction product, play essential role in multiple physiological processes, ranging from synaptic plasticity, hematopoietic cell survival, development and function, to mRNA export, transcriptional regulation and chromatin remodelling. Rather than to provide an unique and “universal” mechanism of Ins(1,3,4,5)P4 action, these studies in genetically-modified mice point for a role of this inositide in the control of calcium mobilization, of the subcellular localisation of PH domain-containing target proteins, and of higher inositol phosphate production. Read More

    Diphosphoinositol polyphosphates: what are the mechanisms?
    Adv Enzyme Regul 2011 28;51(1):13-25. Epub 2010 Oct 28.
    Inositol Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
    In countries where adulthood is considered to be attained at age eighteen, 2011 can be the point at which the diphosphoinositol polyphosphates might formally be described as "coming of age", since these molecules were first fully defined in 1993 (Menniti et al., 1993; Stephens et al., 1993b). Read More

    Involvement of human choline kinase alpha and beta in carcinogenesis: a different role in lipid metabolism and biological functions.
    Adv Enzyme Regul 2011 28;51(1):183-94. Epub 2010 Oct 28.
    Garvan Institute of Medical Research, Sydney NSW, Australia.
    We have summarized here the importance of ChoKα1 in human carcinogenesis. ChoKα1 displays its oncogenic activity through activation of specific signaling pathways that influence on cell proliferation and survival. It is overexpressed in a large number of human tumors with an incidence of 40-60% of all tumors investigated. Read More

    p53 and regulation of bioactive sphingolipids.
    Adv Enzyme Regul 2011 28;51(1):219-28. Epub 2010 Oct 28.
    Department of Medicine, Medical University of South Carolina, Charleston, SC 29425-7790, USA.
    Both the sphingolipid and p53 pathways are important regulators- and apparent collaborators-of cell-fate decisions. Whereas some investigations have suggested that ceramide and more complex sphingolipids function upstream of p53 or in a p53-independent manner, other studies propose that p53-dependent alterations in these sphingolipids can also contribute to apoptosis. Further studies focusing on sphingolipid metabolizing enzymes have revealed that they function similarly both upstream and downstream of p53 activation. Read More

    Capitalizing on tumor genotyping: towards the design of mutation specific inhibitors of phosphoinsitide-3-kinase.
    Adv Enzyme Regul 2011 28;51(1):273-9. Epub 2010 Oct 28.
    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
    PI3Ks catalyze the phosphorylation of the inositol hydroxyls of phosphoinositide membrane components. The changes in phosphorylation of the inositides recruit proteins to the plasma membrane that initiate important signaling cascades. PI3Kα, one of the class IA PI3Ks, is highly mutated in cancers. Read More

    Physiology and pathology of nuclear phospholipase C β1.
    Adv Enzyme Regul 2011 28;51(1):2-12. Epub 2010 Oct 28.
    Cellular Signalling Laboratory, Department of Human Anatomical Sciences, University of Bologna, Bologna, Italy.
    The existence and function of inositide signaling in the nucleus is well documented and we know that the existence of the inositide cycle inside the nucleus has a biological role. An autonomous lipid-dependent signaling system, independently regulated from its plasma membrane counterpart, acts in the nucleus and modulates cell cycle progression and differentiation.We and others focused on PLCβ1, which is the most extensively investigated PLC isoform in the nuclear compartment. Read More

    Phospholipase Cδ3 is a novel binding partner of myosin VI and functions as anchoring of myosin VI on plasma membrane.
    Adv Enzyme Regul 2011 28;51(1):171-81. Epub 2010 Oct 28.
    Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
    Phospholipase Cδ3 (PLCδ3) is a key enzyme in phosphoinositide metabolism, however, its physiological function remains unknown. Here we identified the Myosin VI (Myo6) as a binding partner of the PLCδ3. A tail region containing IQ motif and the cargo-binding domain of Myo6, and the C2 domain and PH domain of PLCδ3 were responsible sites for the interaction. Read More

    Subtype-specific roles of phospholipase C-β via differential interactions with PDZ domain proteins.
    Adv Enzyme Regul 2011 28;51(1):138-51. Epub 2010 Oct 28.
    School of Nano-Biotechnology & Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
    Since we first identified the PLC-β isozyme, enormous studies have been conducted to investigate the functional roles of this protein (Min et al., 1993; Suh et al.,1988). Read More

    The neutral sphingomyelinase family: identifying biochemical connections.
    Adv Enzyme Regul 2011 28;51(1):51-8. Epub 2010 Oct 28.
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
    Neutral sphingomyelinases (N-SMases) are considered to be key mediators of stress-induced ceramide production. The extended family of N-SMases is a subset of the DNaseI superfamily and comprises members from bacteria, yeast and mammals. In recent years, the identification and cloning of mammalian N-SMase family members has led to significant advances in understanding their physiological roles and regulation. Read More

    Targeting the cancer initiating cell: the Achilles' heel of cancer.
    Adv Enzyme Regul 2011 28;51(1):152-62. Epub 2010 Oct 28.
    Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
    We have isolated cell with the cancer initiating cell (CIC) phenotype from PC3 cells. The PC3/(CIC) cells are more resistant than the PC3/(BC) cells to chemotherapeutic drugs such as docetaxel which is used to treat prostate cancer. Thus these prostate CICs could lay dormant and persist even after chemotherapeutic drug treatment. Read More

    Muscular laminopathies: role of prelamin A in early steps of muscle differentiation.
    Adv Enzyme Regul 2011 28;51(1):246-56. Epub 2010 Oct 28.
    Laboratory of Musculoskeletal Cell Biology, Istituto Ortopedico Rizzoli, Bologna, Italy.
    Lamin A is a nuclear envelope constituent involved in a group of human disorders, collectively referred to as laminopathies, which include Emery-Dreifuss muscular dystrophy. Because increasing evidence suggests a role of lamin A precursor in nuclear functions, we investigated the processing of prelamin A along muscle differentiation. Both protein levels and cellular localization of prelamin A appears to be modulated during C2C12 mouse myoblasts activation. Read More

    Sphingolipid metabolism in trans-golgi/endosomal membranes and the regulation of intracellular homeostatic processes in eukaryotic cells.
    Adv Enzyme Regul 2010 23;50(1):339-48. Epub 2009 Dec 23.
    Department of Cell & Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090, USA.

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