335 results match your criteria Advances in biological regulation[Journal]


Exploring the controversial role of PI3K signalling in CD4 regulatory T (T-Reg) cells.

Adv Biol Regul 2020 May 23;76:100722. Epub 2020 Apr 23.

Inositide Laboratory, School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Life Sciences Building 85, Highfield, Southampton, SO17 1BJ, UK.

The immune system is a complex network that acts to protect vertebrates from foreign microorganisms and carries out immunosurveillance to combat cancer. In order to avoid hyper-activation of the immune system leading to collateral damage tissues and organs and to prevent self-attack, the network has the intrinsic control mechanisms that negatively regulate immune responses. Central to this negative regulation are regulatory T (T-Reg) cells, which through cytokine secretion and cell interaction limit uncontrolled clonal expansion and functions of activated immune cells. Read More

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http://dx.doi.org/10.1016/j.jbior.2020.100722DOI Listing

Lipidomics-based assays coupled with computational approaches can identify novel phospholipase A inhibitors.

Adv Biol Regul 2020 May 10;76:100719. Epub 2020 Mar 10.

Department of Chemistry and Biochemistry and Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093-0601, USA. Electronic address:

Phospholipase A (PLA) enzymes play a major role in many diseases including the inflammatory cascade and specific potent small molecule inhibitors could be useful in studying their physiological role as well as for the development of drugs. In order to discover novel small molecule inhibitor platforms for members of the PLA superfamily of enzymes, we have applied computational approaches to determine the binding mode of potent inhibitors specific for particular PLAs to the screening of chemical libraries. This has including the U. Read More

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http://dx.doi.org/10.1016/j.jbior.2020.100719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230010PMC

Modulation of sulfur assimilation metabolic toxicity overcomes anemia and hemochromatosis in mice.

Adv Biol Regul 2020 May 26;76:100694. Epub 2020 Jan 26.

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. Electronic address:

Sulfur assimilation is an essential metabolic pathway that regulates sulfation, amino acid metabolism, nucleotide hydrolysis, and organismal homeostasis. We recently reported that mice lacking bisphosphate 3'-nucleotidase (BPNT1), a key regulator of sulfur assimilation, develop iron-deficiency anemia (IDA) and anasarca. Here we demonstrate two approaches that successfully reduce metabolic toxicity caused by loss of BPNT1: 1) dietary methionine restriction and 2) overproduction of a key transcriptional regulator hypoxia inducible factor 2α (Hif-2a). Read More

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http://dx.doi.org/10.1016/j.jbior.2020.100694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230019PMC

Phosphoinositides in cell proliferation and metabolism.

Adv Biol Regul 2020 01 20;75:100693. Epub 2020 Jan 20.

Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy.

Phosphoinositides (PI) are key players in many trafficking and signaling pathways. Recent advances regarding the synthesis, location and functions of these lipids have improved our understanding of how and when these lipids are generated and what their roles are in physiology and disease. In particular, PI play a central role in the regulation of cell proliferation and metabolism. Read More

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http://dx.doi.org/10.1016/j.jbior.2020.100693DOI Listing
January 2020

Editorial.

Authors:
Lucio Cocco

Adv Biol Regul 2020 01 10;75:100689. Epub 2019 Dec 10.

Bologna, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jbior.2019.100689DOI Listing
January 2020

Roles of DGKs in neurons: Postsynaptic functions?

Adv Biol Regul 2020 01 28;75:100688. Epub 2019 Nov 28.

The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205, USA. Electronic address:

Diacylglycerol kinases (DGKs) contribute to an important part of intracellular signaling because, in addition to reducing diacylglycerol levels, they generate phosphatidic acid (PtdOH) Recent research has led to the discovery of ten mammalian DGK isoforms, all of which are found in the mammalian brain. Many of these isoforms have studied functions within the brain, while others lack such understanding in regards to neuronal roles, regulation, and structural dynamics. However, while previously a neuronal function for DGKθ was unknown, it was recently found that DGKθ is required for the regulation of synaptic vesicle endocytosis and work is currently being conducted to elucidate the mechanism behind this regulation. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056498PMC
January 2020

A two-way switch for inositol pyrophosphate signaling: Evolutionary history and biological significance of a unique, bifunctional kinase/phosphatase.

Adv Biol Regul 2020 01 14;75:100674. Epub 2019 Nov 14.

Signal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. Electronic address:

The inositol pyrophosphates (PP-InsPs) are a unique subgroup of intracellular signals with diverse functions, many of which can be viewed as reflecting an overarching role in metabolic homeostasis. Thus, considerable attention is paid to the enzymes that synthesize and metabolize the PP-InsPs. One of these enzyme families - the diphosphoinositol pentakisphosphate kinases (PPIP5Ks) - provides an extremely rare example of separate kinase and phosphatase activities being present within the same protein. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100674DOI Listing
January 2020

Three dimensional in vitro models of cancer: Bioprinting multilineage glioblastoma models.

Adv Biol Regul 2020 01 17;75:100658. Epub 2019 Oct 17.

Institute of Biological Chemistry, Biophysics & Bioengineering, Heriot Watt University, Edinburgh, UK. Electronic address:

Three dimensional (3D) bioprinting of multiple cell types within optimised extracellular matrices has the potential to more closely model the 3D environment of human physiology and disease than current alternatives. In this study, we used a multi-nozzle extrusion bioprinter to establish models of glioblastoma made up of cancer and stromal cells printed within matrices comprised of alginate modified with RGDS cell adhesion peptides, hyaluronic acid and collagen-1. Methods were developed using U87MG glioblastoma cells and MM6 monocyte/macrophages, whilst more disease relevant constructs contained glioblastoma stem cells (GSCs), co-printed with glioma associated stromal cells (GASCs) and microglia. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100658DOI Listing
January 2020
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Recent advances in MDS mutation landscape: Splicing and signalling.

Adv Biol Regul 2020 01 5;75:100673. Epub 2019 Nov 5.

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Recurrent cytogenetic aberrations, genetic mutations and variable gene expression have been consistently recognized in solid cancers and in leukaemia, including in Myelodysplastic Syndromes (MDS). Besides conventional cytogenetics, the growing accessibility of new techniques has led to a deeper analysis of the molecular significance of genetic variations. Indeed, gene mutations affecting splicing genes, as well as genes implicated in essential signalling pathways, play a pivotal role in MDS physiology and pathophysiology, representing potential new molecular targets for innovative therapeutic strategies. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100673DOI Listing
January 2020

Sphingosine-1-phosphate signaling: A novel target for simultaneous adjuvant treatment of triple negative breast cancer and chemotherapy-induced neuropathic pain.

Adv Biol Regul 2020 01 15;75:100670. Epub 2019 Oct 15.

Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, VA, USA. Electronic address:

Triple-negative breast cancer (TNBC) is very aggressive with high metastatic and mortality rates and unfortunately, except for chemotherapy, there are few therapeutic options. The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) regulates numerous processes important for cancer progression, metastasis, and neuropathic pain. The pro-drug FTY720 (fingolimod, Gilenya) used to treat multiple sclerosis is phosphorylated in the body to a S1P mimic that binds to S1PRs, except S1PR2, and also acts as a functional antagonist of S1PR1. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100670DOI Listing
January 2020

Biological regulation of diacylglycerol kinases in normal and neoplastic tissues: New opportunities for cancer immunotherapy.

Adv Biol Regul 2020 01 30;75:100663. Epub 2019 Oct 30.

Department of Immunology and Oncology, National Center for Biotechnology (CNB-CSIC), Darwin 3, UAM Campus de Cantoblanco, 28049, Madrid, Spain. Electronic address:

In the recent years, the arsenal of anti-cancer therapies has evolved to target T lymphocytes and restore their capacity to destroy tumor cells. However, the clinical success is limited, with a large number of patients that never responds and others that ultimately develop resistances. Overcoming the hypofunctional state imposed by solid tumors to T cells has revealed critical but challenging due to the complex strategies that tumors employ to evade the immune system. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100663DOI Listing
January 2020

Abilities of β-Estradiol to interact with chemotherapeutic drugs, signal transduction inhibitors and nutraceuticals and alter the proliferation of pancreatic cancer cells.

Adv Biol Regul 2020 01 18;75:100672. Epub 2019 Oct 18.

Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, 27858, USA. Electronic address:

Improving the effects of chemotherapy and reducing the side effects are important goals in cancer research. Various approaches have been examined to enhance the effectiveness of chemotherapy. For example, signal transduction inhibitors or hormonal based approaches have been included with chemo- or radio-therapy. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100672DOI Listing
January 2020

Introduction to the special issue on T-cell acute lymphoblastic leukemia genetics, biology and therapeutics.

Authors:
João T Barata

Adv Biol Regul 2019 12 15;74:100671. Epub 2019 Oct 15.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal. Electronic address:

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http://dx.doi.org/10.1016/j.jbior.2019.100671DOI Listing
December 2019
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A high energy phosphate jump - From pyrophospho-inositol to pyrophospho-serine.

Adv Biol Regul 2020 01 8;75:100662. Epub 2019 Oct 8.

Laboratory of Cell Signalling, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, 500039, India. Electronic address:

Inositol pyrophosphates (PP-IPs) are a class of energy rich metabolites present in all eukaryotic cells. The hydroxyl groups on these water soluble derivatives of inositol are substituted with diphosphate and monophosphate moieties. Since the discovery of PP-IPs in the early 1990s, enormous progress has been made in uncovering pleiotropic roles for these small molecules in cellular physiology. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100662DOI Listing
January 2020
3 Reads

Induction of membrane curvature by proteins involved in Golgi trafficking.

Adv Biol Regul 2020 01 16;75:100661. Epub 2019 Oct 16.

Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA, 92093, USA. Electronic address:

The Golgi apparatus serves a key role in processing and sorting lipids and proteins for delivery to their final cellular destinations. Vesicle exit from the Golgi initiates with directional deformation of the lipid bilayer to produce a bulge. Several mechanisms have been described by which lipids and proteins can induce directional membrane curvature to promote vesicle budding. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056495PMC
January 2020

Illuminating insights into opsin 3 function in the skin.

Adv Biol Regul 2020 01 7;75:100668. Epub 2019 Oct 7.

Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence RI, 02912, USA. Electronic address:

Because sunlight is essential for human survival, we have developed complex mechanisms for detecting and responding to light stimuli. The eyes and skin are major organs for sensing light and express several light-sensitive opsin receptors. These opsins mediate cellular responses to spectrally-distinct wavelengths of visible and ultraviolet light. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059126PMC
January 2020

Structural analyses of inositol phosphate second messengers bound to signaling effector proteins.

Authors:
Raymond D Blind

Adv Biol Regul 2020 01 11;75:100667. Epub 2019 Oct 11.

Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, USA; Department of Biochemistry, Vanderbilt University School of Medicine, USA; Department of Pharmacology, Vanderbilt University School of Medicine, USA. Electronic address:

The higher-order inositol phosphate second messengers inositol tetrakisphosphate (IP4), inositol pentakisphosphate (IP5) and inositol hexakisphosphate (IP6) are important signaling molecules that regulate DNA-damage repair, cohesin dynamics, RNA-editing, retroviral assembly, nuclear transport, phosphorylation, acetylation, crotonylation, and ubiquitination. This functional diversity has made understanding how inositol polyphosphates regulate cellular processes challenging to dissect. However, some inositol phosphates have been unexpectedly found in X-ray crystal structures, occasionally revealing structural and mechanistic details of effector protein regulation before functional consequences have been described. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056587PMC
January 2020

MicroRNA dysregulation and multi-targeted therapy for cancer treatment.

Adv Biol Regul 2020 01 13;75:100669. Epub 2019 Oct 13.

Department of Cancer Biology and Genetics and Comprehensive Cancer Center at the Wexner Medical Center, The Ohio State University, Columbus, OH, USA. Electronic address:

We established that loss of miR-15a/16-1 genes on chromosome 13q14 is the most common alteration in Chronic Lymphocytic Leukemia (CLL) and that miR-15/16 are crucial negative regulator of BCL-2, an antiapoptotic gene overexpressed in most CLLs and in many other malignancies. We have also shown that miR-15/16 target ROR1, a cell surface receptor for Wnt5a which can enhance growth/survival of CLL cells. Interestingly, ROR1 is expressed by many cancers, but not by normal adult tissues. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056524PMC
January 2020
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Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update.

Adv Biol Regul 2020 01 7;75:100660. Epub 2019 Oct 7.

IRIBHM, Campus Erasme, ULB Bâtiment C, 808 Route de Lennik, 1070, Bruxelles, Belgium. Electronic address:

Phosphoinositides (PIs) are phosphorylated derivatives of phosphatidylinositol. They act as signaling molecules linked to essential cellular mechanisms in eukaryotic cells, such as cytoskeleton organization, mitosis, polarity, migration or invasion. PIs are phosphorylated and dephosphorylated by a large number of PI kinases and PI phosphatases acting at the 5-, 4- and 3- position of the inositol ring. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100660DOI Listing
January 2020
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Oncogenic protein kinase Cι signaling mechanisms in lung cancer: Implications for improved therapeutic strategies.

Adv Biol Regul 2020 01 25;75:100656. Epub 2019 Sep 25.

From the Department of Cancer Cell Biology, Mayo Clinic Florida, Jacksonville, FL, 32224, USA. Electronic address:

Protein Kinase Cι (PKCι) is a major oncogene involved in the initiation, maintenance and progression of numerous forms of human cancer. In the lung, PKCι is necessary for the maintenance of the transformed phenotype of the two major forms of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC). In addition, PKCι is necessary for both LADC and LSCC tumorigenesis by establishing and maintaining a highly aggressive stem-like, tumor-initiating cell phenotype. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100656DOI Listing
January 2020

Cellular signaling and epigenetic regulation of gene expression in leukemia.

Adv Biol Regul 2020 01 5;75:100665. Epub 2019 Oct 5.

Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, USA. Electronic address:

Alterations in normal regulation of gene expression is one of the key features of hematopoietic malignancies. In order to gain insight into the mechanisms that regulate gene expression in these diseases, we dissected the role of the Ikaros protein in leukemia. Ikaros is a DNA-binding, zinc finger protein that functions as a transcriptional regulator and a tumor suppressor in leukemia. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239353PMC
January 2020

HOIL-1, an atypical E3 ligase that controls MyD88 signalling by forming ester bonds between ubiquitin and components of the Myddosome.

Adv Biol Regul 2020 01 5;75:100666. Epub 2019 Oct 5.

MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, United Kingdom.

Components of bacteria and viruses activate Toll-Like Receptors in host cells, triggering the formation of the Myddosome and a signalling network that culminates in the production and release of the inflammatory mediators required to combat pathogenic infection. The Myddosome initiates signalling by recruiting and activating five E3 ligases that generate hybrid ubiquitin chains and attach them to components of the Myddosome. These ubiquitin chains act as a scaffold for the recruitment and activation of ubiquitin-binding proteins, which include the "master" protein kinases TAK1 and IKKβ that drive inflammatory mediator production, as well as other proteins like ABIN1 and A20 that restrict activation of the network to prevent the overproduction of these substances that can lead to autoimmunity and organ damage. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132539PMC
January 2020

Class I phosphoinositide 3-kinase (PI3K) regulatory subunits and their roles in signaling and disease.

Adv Biol Regul 2020 01 28;75:100657. Epub 2019 Sep 28.

Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, V8W 2Y2, Canada. Electronic address:

The Class I phosphoinositide 3-kinases (PI3Ks) are a group of heterodimeric lipid kinases that regulate crucial cellular processes including proliferation, survival, growth, and metabolism. The diversity in functions controlled by the various catalytic isoforms (p110α, p110β, p110δ, and p110γ) depends on their abilities to be activated by distinct stimuli such as receptor tyrosine kinases (RTKs), G-protein coupled receptors (GPCRs), and the Ras family of small G-proteins. A major factor determining the ability of each p110 enzyme to be activated is the presence of regulatory binding partners. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100657DOI Listing
January 2020

Mice lacking DGKε show increased beige adipogenesis in visceral white adipose tissue after long-term high fat diet in a COX-2- dependent manner.

Adv Biol Regul 2020 01 5;75:100659. Epub 2019 Oct 5.

Department of Anatomy and Cell Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata City, Yamagata, 9909585, Japan.

Adipose tissue is a central site for energy storage in the form of triglyceride (TG). Under excess energy conditions, TG is synthesized by acylation of diacylglycerol (DG), whereas TG is broken down into DG and free fatty acid, which provide energy for mitochondrial lipid oxidation when needed. In this regard, DG is not merely an intermediate metabolite for TG metabolism; it also serves as a signaling molecule. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100659DOI Listing
January 2020
1 Read

Phosphatidylinositol 3 monophosphate metabolizing enzymes in blood platelet production and in thrombosis.

Adv Biol Regul 2020 01 7;75:100664. Epub 2019 Oct 7.

Inserm U1048 and Université Paul Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Laboratoire d'Hématologie, Hopital Universitaire de Toulouse, Toulouse, France. Electronic address:

Blood platelets, produced by the fragmentation of megakaryocytes, play a key role in hemostasis and thrombosis. Being implicated in atherothrombosis and other thromboembolic disorders, they represent a major therapeutic target for antithrombotic drug development. Several recent studies have highlighted an important role for the lipid phosphatidylinositol 3 monophosphate (PtdIns3P) in megakaryocytes and platelets. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100664DOI Listing
January 2020
1 Read

NSAID therapy for PIK3CA-Altered colorectal, breast, and head and neck cancer.

Adv Biol Regul 2020 01 15;75:100653. Epub 2019 Sep 15.

Department of Otolaryngology - Head and Neck Surgery, University of California, San Francisco, San Francisco, CA, USA. Electronic address:

Epidemiologic evidence indicates that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) provides a protective effect against the development of colorectal, breast, and head and neck cancers. Genomic characterization of these cancers has lent considerable insight into the subpopulations of cancer patients who are most likely to benefit from NSAID therapy. The PIK3CA gene encodes the catalytic subunit of phosphatidylinositol 3-kinase (PI3K) and is among the most frequently mutated genes in solid tumor malignancies. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056575PMC
January 2020
1 Read

Splicing factor mutant myelodysplastic syndromes: Recent advances.

Adv Biol Regul 2020 01 19;75:100655. Epub 2019 Sep 19.

Bloodwise Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford BRC Haematology Theme, Oxford, UK. Electronic address:

The myelodysplastic syndromes (MDS) are common myeloid malignancies showing frequent progression to acute myeloid leukemia (AML). Pre-mRNA splicing is an essential cellular process carried out by the spliceosome. Mutations in splicing factor genes (including SF3B1, SRSF2, U2AF1 and ZRSR2) occur in over half of MDS patients and result in aberrant pre-mRNA splicing of many target genes, implicating aberrant spliceosome function in MDS disease pathogenesis. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100655DOI Listing
January 2020
1 Read

The function of PLCγ1 in developing mouse mDA system.

Adv Biol Regul 2020 01 19;75:100654. Epub 2019 Sep 19.

School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, 689-798, South Korea; Korea Brain Research Institute, Daegu, 41062, South Korea. Electronic address:

During neural development, growing neuronal cells consistently sense and communicate with their surroundings through the use of signaling molecules. In this process, spatiotemporally well-coordinated intracellular signaling is a prerequisite for proper neuronal network formation. Thus, intense interest has focused on investigating the signaling mechanisms in neuronal structure formation that link the activation of receptors to the control of cell shape and motility. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100654DOI Listing
January 2020

MicroRNAs and their involvement in T-ALL: A brief overview.

Adv Biol Regul 2019 12 5;74:100650. Epub 2019 Sep 5.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisbon, Portugal. Electronic address:

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy in which the transformed clone is arrested during T-cell development. Several genetic and epigenetic events have been implicated in this transformation. MicroRNAs (miRNAs) are small, non-coding RNAs that primarily function as endogenous translational repressors of protein-coding genes. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899521PMC
December 2019
1 Read

Insulin-like growth factor (IGF) signaling in T-cell acute lymphoblastic leukemia.

Adv Biol Regul 2019 12 15;74:100652. Epub 2019 Sep 15.

Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, V5Z 1L3, Canada. Electronic address:

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer, characterized by an uncontrolled expansion and accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and occupy the bone marrow compartment, thereby interfering with the production of normal blood cells. Pediatric T-ALL is curable with intensive chemotherapy, but there are significant, long-term side effects and ~20% of patients suffer relapse for which there are limited treatment options. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100652DOI Listing
December 2019
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New advances in targeting aberrant signaling pathways in T-cell acute lymphoblastic leukemia.

Adv Biol Regul 2019 12 5;74:100649. Epub 2019 Sep 5.

Institute of Molecular Genetics, Luigi Luca Cavalli-Sforza-CNR National Research Council of Italy, Bologna, Italy; IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. Electronic address:

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disorder characterized by malignant transformation of immature progenitors primed towards T-cell development. Over the past 15 years, advances in the molecular characterization of T-ALL have uncovered oncogenic key drivers and crucial signaling pathways of this disease, opening new chances for the development of novel therapeutic strategies. Currently, T-ALL patients are still treated with aggressive therapies, consisting of high dose multiagent chemotherapy. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100649DOI Listing
December 2019
1 Read

Multi-omic approaches to improve outcome for T-cell acute lymphoblastic leukemia patients.

Adv Biol Regul 2019 12 26;74:100647. Epub 2019 Aug 26.

Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. Electronic address:

In the last decade, tremendous progress in curative treatment has been made for T-ALL patients using high-intensive, risk-adapted multi-agent chemotherapy. Further treatment intensification to improve the cure rate is not feasible as it will increase the number of toxic deaths. Hence, about 20% of pediatric patients relapse and often die due to acquired therapy resistance. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100647DOI Listing
December 2019
1 Read

Altered chondrocyte differentiation, matrix mineralization and MEK-Erk1/2 signaling in an INPPL1 catalytic knock-out mouse model of opsismodysplasia.

Adv Biol Regul 2020 May 5;76:100651. Epub 2019 Sep 5.

Laboratory of Functional Genetics, GIGA-Molecular Biology of Disease, GIGA-B34, CHU Sart-Tilman, University of Liège, avenue de l'Hôpital 11, 4000, Liège, Belgium. Electronic address:

Opsismodysplasia (OPS) is a rare but severe autosomal recessive skeletal chondrodysplasia caused by inactivating mutations in the Inppl1/Ship2 gene. The molecular mechanism leading from Ship2 gene inactivation to OPS is currently unknown. Here, we used our Ship2 mouse expressing reduced amount of a catalytically-inactive SHIP2 protein and a previously reported SHIP2 inhibitor to investigate growth plate development and mineralization in vivo, ex vivo and in vitro. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100651DOI Listing

Protein-protein interaction analysis highlights the role of septins in membrane enclosed lumen and mRNA processing.

Adv Biol Regul 2019 08 27;73:100635. Epub 2019 Jul 27.

INSERM, Unité 1193, Villejuif, F-94800, France; Université Paris-Sud, UMR-S 1193, Villejuif, F-94800, France. Electronic address:

Septins are a family of GTP-binding proteins that assemble into non-polar filaments which can be recruited to negatively charged membranes and serve as a scaffold to recruit cytosolic proteins and cytoskeletal elements such as microtubules and actin so that they can perform their important biological functions. Human septins consist of four groups, each with 13 members, and filaments formation usually involve members from each group in specific positions. However, little is known about the molecular mechanisms that drive the binding of septins to membranes and its importance to their biological functions. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100635DOI Listing

The role of phospholipase Cβ on the plasma membrane and in the cytosol: How modular domains enable novel functions.

Authors:
Suzanne Scarlata

Adv Biol Regul 2019 08 29;73:100636. Epub 2019 Jul 29.

Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 100 Institute Rd., Worcester, MA, 01609, United States. Electronic address:

Phospholipase Cβ (PLCβ) is a signaling enzyme activated by G proteins to generate calcium signals. The catalytic core of PLCβ is surrounded by modular domains that mediate the interaction of the enzyme with known protein partners on the plasma membrane. The C-terminal region PLCβ contains a novel coiled-coil domain that is required for Gαq binding and activation. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732780PMC

ZEB2 in T-cells and T-ALL.

Adv Biol Regul 2019 12 27;74:100639. Epub 2019 Jul 27.

Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address:

The identification of the rare but recurrent t(2; 14)(q22; q32) translocation involving the ZEB2 locus in T-cell acute lymphoblastic leukemia, suggested that ZEB2 is an oncogenic driver of this high-risk subtype of leukemia. ZEB2, a zinc finger E-box homeobox binding transcription factor, is a master regulator of cellular plasticity and its expression is correlated with poor overall survival of cancer patients. Recent loss- and gain-of-function in the mouse revealed important roles of ZEB2 during different stages of hematopoiesis, including the T-cell lineage. Read More

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December 2019
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The TCR/CD3 complex in leukemogenesis and as a therapeutic target in T-cell acute lymphoblastic leukemia.

Adv Biol Regul 2019 12 27;74:100638. Epub 2019 Jul 27.

Institut Curie, PSL Research University, CNRS UMR 3348, F-91405, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR 3348, F-91405, Orsay, France. Electronic address:

T-cell acute lymphoblastic leukemia (T-ALL) arises from T cell precursors and is characterized by expression of many lineage-specific proteins. While T-cell antigen receptor (TCR) signaling and its strength are central for thymocyte development, mature T cell homeostasis and immune responses, their roles in T-ALL remain undetermined. Indeed, in contrast to mouse models, in which absence of TCR or major histocompatibility complex binding does not impact on leukemogenesis, other mouse models suggest that basal or weak signaling drives leukemia development. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100638DOI Listing
December 2019
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Desperately seeking a home marrow niche for T-cell acute lymphoblastic leukaemia.

Adv Biol Regul 2019 12 27;74:100640. Epub 2019 Jul 27.

UMRE008 Stabilité Génétique Cellules Souches et Radiations, U1274 Inserm, Université de Paris, Université Paris-Saclay, CEA, F-92260 Fontenay-aux-Roses, France; Laboratory of Hematopoietic Stem Cells and Leukemia, Team Niche and Cancer in Hematopoiesis, U1274, Inserm, CEA, 18 route du panorama, 92260, Fontenay-aux-Roses, France; Laboratoire labellisé par l'Association pour la Recherche sur le Cancer, France. Electronic address:

T-cell acute leukemia is a hematologic malignancy that results from the progressive acquisition of genomic abnormalities in T-cell progenitors/precursors. T-ALL is commonly thought to originate from the thymus albeit recent literature describes the possible acquisition of the first oncogenic hits in hematopoietic progenitor cells of the bone marrow (BM). The journey of T-ALL from its arising to full blown expansion meets different microenvironments, including the BM in which leukemic cells settle down early after the disease spreading. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100640DOI Listing
December 2019
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A synthetic biological approach to reconstitution of inositide signaling pathways in bacteria.

Adv Biol Regul 2019 08 30;73:100637. Epub 2019 Jul 30.

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA. Electronic address:

Inositide lipid (PIP) and soluble (IP) signaling pathways produce essential cellular codes conserved in eukaryotes. In many cases, deconvoluting metabolic and functional aspects of individual pathways are confounded by promiscuity and multiplicity of PIP and IP kinases and phosphatases. We report a molecular genetic approach that reconstitutes eukaryotic inositide lipid and soluble pathways in a prokaryotic cell which inherently lack inositide kinases and phosphatases in their genome. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216163PMC
August 2019
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ABCC3 is a novel target for the treatment of pancreatic cancer.

Adv Biol Regul 2019 08 24;73:100634. Epub 2019 Apr 24.

Metabolic Signalling Group, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, 6102, Perth, WA, Australia; Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Blizard Institute, Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK. Electronic address:

Pancreatic Ductal Adenocarcinoma (PDAC) is a very aggressive disease, lacking effective therapeutic approaches and leaving PDAC patients with a poor prognosis. The life expectancy of PDAC patients has not experienced a significant change in the last few decades with a five-year survival rate of only 8%. To address this unmet need, novel pharmacological targets must be identified for clinical intervention. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.04.004DOI Listing
August 2019
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Abilities of berberine and chemically modified berberines to interact with metformin and inhibit proliferation of pancreatic cancer cells.

Adv Biol Regul 2019 08 21;73:100633. Epub 2019 Apr 21.

Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, 27858, USA. Electronic address:

Pancreatic cancer is devastating cancer worldwide with few if any truly effective therapies. Pancreatic cancer has an increasing incidence and may become the second leading cause of death from cancer. Novel, more effective therapeutic approaches are needed as pancreatic cancer patients usually survive for less than a year after being diagnosed. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.04.003DOI Listing
August 2019
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Diverse signaling mechanisms of mTOR complexes: mTORC1 and mTORC2 in forming a formidable relationship.

Adv Biol Regul 2019 05 11;72:51-62. Epub 2019 Apr 11.

Department of Neurosurgery, Westchester Medical Center / New York Medical College, Valhalla, NY, 10595, USA.

Activation of Mechanistic target of rapamycin (mTOR) signaling plays a crucial role in tumorigenesis of numerous malignancies including glioblastoma (GB). The Canonical PI3K/Akt/mTOR signaling cascade is commonly upregulated due to loss of the tumor suppressorm PTEN, a phosphatase that acts antagonistically to the kinase (PI3K) in conversion of PIP2 to PIP3. mTOR forms two multiprotein complexes, mTORC1 and mTORC2 which are composed of discrete protein binding partners to regulate cell growth, motility, and metabolism. Read More

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May 2019
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Polyphosphoinositides in the nucleus: Roadmap of their effectors and mechanisms of interaction.

Adv Biol Regul 2019 05 6;72:7-21. Epub 2019 Apr 6.

Department of Biological Sciences, University of Bergen, Bergen, 5008, Norway. Electronic address:

Biomolecular interactions between proteins and polyphosphoinositides (PPIn) are essential in the regulation of the vast majority of cellular processes. Consequently, alteration of these interactions is implicated in the development of many diseases. PPIn are phosphorylated derivatives of phosphatidylinositol and consist of seven species with different phosphate combinations. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.04.001DOI Listing
May 2019
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Phosphoinositide spatially free AKT/PKB activation to all membrane compartments.

Adv Biol Regul 2019 05 11;72:1-6. Epub 2019 Apr 11.

University of Wisconsin-Madison, School of Medicine and Public Health, 1300 University Ave, Madison, WI, 53706, USA. Electronic address:

Ser and Thr kinase AKT also known as protein kinase B (PKB) was discovered more than two and half decades ago and is one of the key downstream molecules in the phosphoinositide 3-kinase signaling pathways. The pleiotropic effects of this kinase have attracted intense interest and limelight in cancer biology, cancer therapy, diabetes, and cardiovascular diseases. Authors may refer to other more comprehensive and recent reviews on AKT/PKB (Manning and Cantley, 2007; Manning and Toker, 2017). Read More

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http://dx.doi.org/10.1016/j.jbior.2019.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529224PMC
May 2019
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Effects of the MDM-2 inhibitor Nutlin-3a on PDAC cells containing and lacking WT-TP53 on sensitivity to chemotherapy, signal transduction inhibitors and nutraceuticals.

Adv Biol Regul 2019 05 15;72:22-40. Epub 2019 Mar 15.

Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA, 27834. Electronic address:

Mutations at the TP53 gene are readily detected (approximately 50-75%) in pancreatic ductal adenocarcinoma (PDAC) patients. TP53 was previously thought to be a difficult target as it is often mutated, deleted or inactivated on both chromosomes in certain cancers. In the following study, the effects of restoration of wild-type (WT) TP53 activity on the sensitivities of MIA-PaCa-2 pancreatic cancer cells to the MDM2 inhibitor nutlin-3a in combination with chemotherapy, targeted therapy, as well as, nutraceuticals were examined. Read More

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May 2019
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Fructose-1,6-bisphosphatase: From a glucose metabolism enzyme to multifaceted regulator of a cell fate.

Adv Biol Regul 2019 05 9;72:41-50. Epub 2019 Mar 9.

Department of Molecular Physiology and Neurobiology, Wroclaw University, Wroclaw, Poland. Electronic address:

Fructose-1,6-bisphosphatase (FBPase) is one of the ancient, evolutionarily conserved enzymes of carbohydrate metabolism. It has been described for a first time in 1943, however, for the next half a century mostly kinetic and structural parameters of animal FBPases have been studied. Discovery of ubiquitous expression of the muscle isozyme of FBPase, thus far considered to merely regulate glycogen synthesis from carbohydrate precursors, and its nuclear localisation in several cell types has risen new interest in the protein, resulting in numerous publications revealing complex functions/properties of FBPase. Read More

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May 2019
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Pancreatic cancer tumorspheres are cancer stem-like cells with increased chemoresistance and reduced metabolic potential.

Adv Biol Regul 2019 05 23;72:63-77. Epub 2019 Feb 23.

Metabolic Signalling Group, School of Pharmacy & Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, 6102, Australia. Electronic address:

Cancer stem cells are a population of slow-cycling cells within the tumour bulk, with self-renewal capacity that attracts interest as a therapeutic target. In highly heterogeneous tumours, like pancreatic ductal adenocarcinoma (PDAC) however, the characterisation of cancer stem cells has led to controversial results due to the lack of consensus on specific markers. Here we investigated the characteristics of a population of pancreatic cancer tumorspheres derived from different human pancreatic cancer cell lines and a primary line from a genetically engineered KPC mouse model, using flow cytometry and western blotting to analyse surface and stemness markers. Read More

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May 2019
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Crosstalk between Ras and inositol phosphate signaling revealed by lithium action on inositol monophosphatase in Schizophyllum commune.

Adv Biol Regul 2019 05 3;72:78-88. Epub 2019 Jan 3.

Friedrich Schiller University Jena, Institute of Microbiology, Jena, Germany. Electronic address:

Mushroom forming basidiomycete Schizophyllum commune has been used as a tractable model organism to study fungal sexual development. Ras signaling activation via G-protein-coupled receptors (GPCRs) has been postulated to play a significant role in the mating and development of S. commune. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520614PMC
May 2019
32 Reads

Noncoding RNA genes in cancer pathogenesis.

Adv Biol Regul 2019 01 13;71:219-223. Epub 2018 Dec 13.

Department of Cancer Biology and Genetics, The Wexner Medical Center, Columbus, OH, USA. Electronic address:

By using chronic lymphocytic leukemia as target for discovery in cancer pathogenesis we discovered that the great majority of CLLs (75-85%) carry a deletion of miR-15a and miR-16-1 at 13q14. We also discovered that miR-15/16 are negative regulators of the BCL2 oncogene. Thus the loss of the two negative regulators causes BCL2 overexpression and leukemia. Read More

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http://dx.doi.org/10.1016/j.jbior.2018.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800108PMC
January 2019
26 Reads

A novel role for DGATs in cancer.

Adv Biol Regul 2019 05 13;72:89-101. Epub 2018 Dec 13.

Stony Brook Cancer Center and the Department of Medicine, Stony Brook University, Health Sciences Center, Stony Brook, NY, 11794, USA; The Northport VA Medical Center, Northport, NY, 11768, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jbior.2018.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488436PMC
May 2019
2 Reads