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Advances in Biological Regulation

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https://www.readbyqxmd.com/read/27866974/sphingolipids-in-neutrophil-function-and-inflammatory-responses-mechanisms-and-implications-for-intestinal-immunity-and-inflammation-in-ulcerative-colitis
#1
REVIEW
Mel Pilar Espaillat, Richard R Kew, Lina M Obeid
Bioactive sphingolipids are regulators of immune cell function and play critical roles in inflammatory conditions including ulcerative colitis. As one of the major forms of inflammatory bowel disease, ulcerative colitis pathophysiology is characterized by an aberrant intestinal inflammatory response that persists causing chronic inflammation and tissue injury. Innate immune cells play an integral role in normal intestinal homeostasis but their dysregulation is thought to contribute to the pathogenesis of ulcerative colitis...
November 14, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27838257/phospholipid-regulation-of-the-nuclear-receptor-superfamily
#2
REVIEW
Mark K Crowder, Corey D Seacrist, Raymond D Blind
Nuclear receptors are ligand-activated transcription factors whose diverse biological functions are classically regulated by cholesterol-based small molecules. Over the past few decades, a growing body of evidence has demonstrated that phospholipids and other similar amphipathic molecules can also specifically bind and functionally regulate the activity of certain nuclear receptors, suggesting a critical role for these non-cholesterol-based molecules in transcriptional regulation. Phosphatidylcholines, phosphoinositides and sphingolipids are a few of the many phospholipid like molecules shown to quite specifically regulate nuclear receptors in mouse models, cell lines and in vitro...
October 29, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27776975/machineries-regulating-the-activity-of-the-small-gtpase-arf6-in-cancer-cells-are-potential-targets-for-developing-innovative-anti-cancer-drugs
#3
Yohei Yamauchi, Yuki Miura, Yasunori Kanaho
The Small GTPase ADP-ribosylation factor 6 (Arf6) functions as the molecular switch in cellular signaling pathways by cycling between GDP-bound inactive and GTP-bound active form, which is precisely regulated by two regulators, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Numerous studies have shown that these machineries play critical roles in tumor angiogenesis/growth and cancer cell invasion/metastasis through regulating the cycling of Arf6. Here, we summarize accumulating knowledge for involvement of Arf6 GEFs/GAPs and small molecule inhibitors of Arf6 signaling/cycling in cancer progression, and discuss possible strategies for developing innovative anti-cancer drugs targeting Arf6 signaling/cycling...
October 18, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27776973/plc-%C3%AE-1-and-cell-differentiation-an-insight-into-myogenesis-and-osteogenesis
#4
Giulia Ramazzotti, Irene Faenza, Roberta Fiume, Anna Maria Billi, Lucia Manzoli, Sara Mongiorgi, Stefano Ratti, James A McCubrey, Pann-Ghill Suh, Lucio Cocco, Matilde Y Follo
Phosphoinositide-phospholipase C-β1 (PLC-β1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation and osteogenesis. During myogenic differentiation of murine C2C12 myoblasts, PLC-β1 signaling pathway involves the Inositol Polyphosphate Multikinase (IPMK) and β-catenin as downstream effectors. By means of c-jun binding to cyclin D3 promoter, the activation of PLC-β1 pathway determines cyclin D3 accumulation. However, osteogenesis requires PLC-β1 expression and up-regulation but it does not affect cyclin D3 levels, suggesting that the two processes require the activation of different mediators...
October 18, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27776974/the-significance-of-the-1-kinase-1-phosphatase-activities-of-the-ppip5k-family
#5
Stephen B Shears, Brandi M Baughman, Chunfang Gu, Vasudha S Nair, Huanchen Wang
The inositol pyrophosphates (diphosphoinositol polyphosphates), which include 1-InsP7, 5-InsP7, and InsP8, are highly 'energetic' signaling molecules that play important roles in many cellular processes, particularly with regards to phosphate and bioenergetic homeostasis. Two classes of kinases synthesize the PP-InsPs: IP6Ks and PPIP5Ks. The significance of the IP6Ks - and their 5-InsP7 product - has been widely reported. However, relatively little is known about the biological significance of the PPIP5Ks. The purpose of this review is to provide an update on developments in our understanding of key features of the PPIP5Ks, which we believe strengthens the hypothesis that their catalytic activities serve important cellular functions...
October 17, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27771292/ceramidases-roles-in-sphingolipid-metabolism-and-in-health-and-disease
#6
Nicolas Coant, Wataru Sakamoto, Cungui Mao, Yusuf A Hannun
Over the past three decades, extensive research has been able to determine the biologic functions for the main bioactive sphingolipids, namely ceramide, sphingosine, and sphingosine 1-phosphate (S1P) (Hannun, 1996; Hannun et al., 1986; Okazaki et al., 1989). These studies have managed to define the metabolism, regulation, and function of these bioactive sphingolipids. This emerging body of literature has also implicated bioactive sphingolipids, particularly S1P and ceramide, as key regulators of cellular homeostasis...
October 11, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27776972/roles-of-tp53-in-determining-therapeutic-sensitivity-growth-cellular-senescence-invasion-and-metastasis
#7
James A McCubrey, Kvin Lertpiriyapong, Timothy L Fitzgerald, Alberto M Martelli, Lucio Cocco, Dariusz Rakus, Agnieszka Gizak, Massimo Libra, Melchiorre Cervello, Guiseppe Montalto, Li V Yang, Stephen L Abrams, Linda S Steelman
TP53 is a critical tumor suppressor gene that regulates cell cycle progression, apoptosis, cellular senescence and many other properties critical for control of normal cellular growth and death. Due to the pleiotropic effects that TP53 has on gene expression and cellular physiology, mutations at this tumor suppressor gene result in diverse physiological effects. T53 mutations are frequently detected in numerous cancers. The expression of TP53 can be induced by various agents used to treat cancer patients such as chemotherapeutic drugs and ionizing radiation...
October 6, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27720306/epigenetic-regulation-of-pro-inflammatory-cytokine-secretion-by-sphingosine-1-phosphate-s1p-in-acute-lung-injury-role-of-s1p-lyase
#8
David L Ebenezer, Panfeng Fu, Vidyani Suryadevara, Yutong Zhao, Viswanathan Natarajan
Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes...
September 29, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27717713/biophysical-approaches-promote-advances-in-the-understanding-of-von-willebrand-factor-processing-and-function
#9
Achim Löf, Jochen P Müller, Martin Benoit, Maria A Brehm
The large multimeric plasma glycoprotein von Willebrand factor (VWF) is essential for primary hemostasis by recruiting platelets to sites of vascular injury. VWF multimers respond to elevated hydrodynamic forces by elongation, thereby increasing their adhesiveness to platelets. Thus, the activation of VWF is force-induced, as is its inactivation. Due to these attributes, VWF is a highly interesting system from a biophysical point of view, and is well suited for investigation using biophysical approaches. Here, we give an overview on recent studies that predominantly employed biophysical methods to gain novel insights into multiple aspects of VWF: Electron microscopy was used to shed light on the domain structure of VWF and the mechanism of VWF secretion...
September 28, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27720134/l-plastin-regulates-the-stability-of-the-immune-synapse-of-naive-and-effector-t-cells
#10
Guido Wabnitz, Emre Balta, Yvonne Samstag
T-cells need to be tightly regulated during their activation and effector phase to assure an appropriate defence against cancer or pathogens and - vice versa - to avoid autoimmune reactions. Regulatory signals are provided via the immune synapse between T-cells and antigen-presenting cells (APCs) or target cells. The stability and kinetics of immune synapse formation is critical for proper T-cell functions. It requires dynamic rearrangements of the actin cytoskeleton necessary for organized spatio-temporal redistribution of receptors and adhesion molecules...
September 27, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27707630/phospholipase-c%C3%AE-in-toll-like-receptor-mediated-inflammation-and-innate-immunity
#11
Yoe-Sik Bae, Ha Young Lee, Young Su Jung, Mingyu Lee, Pann-Ghill Suh
Among the phospholipase C (PLC) isoforms, PLCγ not only has unique structural characteristics in terms of harboring SH2 and SH3 domains but also mediates growth factor-induced signaling pathways. PLCγ isoforms are expressed in several innate immune cell types, including macrophages, natural killer cells, mast cells, and neutrophils. Stimulation of Fc receptor or integrin in innate immune cells induces PLCγ activation, which leads to phosphoinositide hydrolysis and calcium increase. The products of PLCγ activity mediate the innate immune response by regulating respiratory burst, phagocytosis, cell adhesion, and cell migration...
September 27, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27773744/fhit-and-wwox-loss-associated-genome-instability-a-genome-caretaker-one-two-punch
#12
Morgan S Schrock, Jenna R Karras, Matthew J Guggenbiller, Teresa Druck, Bahadir Batar, Kay Huebner
Expression of Fhit and Wwox protein is frequently lost or reduced in many human cancers. In this report, we provide data that further characterizes the molecular consequences of Fhit loss in the initiation of DNA double-strand breaks (DSBs), and of Wwox loss in altered repair of DSBs. We show that loss of Fhit initiates mild genome instability in early passage mouse kidney cells, confirming that DNA damage associated with Fhit-deficiency is not limited to cancer cells. We also demonstrate that the cause of Fhit-deficient DSBs: thymidine deficiency-induced replication stress, can be resolved with thymidine supplementation in early passage mouse kidney cells before extensive genome instability occurs...
September 26, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27697466/diacylglycerol-kinases-in-cancer
#13
Isabel Mérida, Pedro Torres-Ayuso, Antonia Ávila-Flores, Javier Arranz-Nicolás, Elena Andrada, María Tello-Lafoz, Rosa Liébana, Raquel Arcos
Diacylglycerol kinases (DGK) are a family of enzymes that catalyze the transformation of diacylglycerol into phosphatidic acid. In T lymphocytes, DGKα and ζ limit the activation of the PLCγ/Ras/ERK axis, providing a critical checkpoint to inhibit T cell responses. Upregulation of these isoforms limits Ras activation, leading to hypo-responsive, anergic states similar to those caused by tumors. Recent studies have identified DGKα upregulation in tumor lymphocyte infiltrates, and cells from DGKα and ζ deficient mice show enhanced antitumor activity, suggesting that limitation of DAG based signals by DGK is used by tumors to evade immune attack...
September 23, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27671966/phosphatidic-acid-and-neurotransmission
#14
Daniel M Raben, Casey N Barber
Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH)...
September 20, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27666503/regulation-of-cellular-proliferation-in-acute-lymphoblastic-leukemia-by-casein-kinase-ii-ck2-and-ikaros
#15
Chandrika Gowda, Chunhua Song, Malika Kapadia, Jonathon L Payne, Tommy Hu, Yali Ding, Sinisa Dovat
The IKZF1 gene encodes the Ikaros protein, a zinc finger transcriptional factor that acts as a master regulator of hematopoiesis and a tumor suppressor in leukemia. Impaired activity of Ikaros is associated with the development of high-risk acute lymphoblastic leukemia (ALL) with a poor prognosis. The molecular mechanisms that regulate Ikaros' function as a tumor suppressor and regulator of cellular proliferation are not well understood. We demonstrated that Ikaros is a substrate for Casein Kinase II (CK2), an oncogenic kinase that is overexpressed in ALL...
September 18, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27666502/wanted-dead-or-alive-myotubularins-a-large-disease-associated-protein-family
#16
Matthieu A Raess, Sylvie Friant, Belinda S Cowling, Jocelyn Laporte
Myotubularins define a large family of proteins conserved through evolution. Several members are mutated in different neuromuscular diseases including centronuclear myopathies and Charcot-Marie-Tooth (CMT) neuropathies, or are linked to a predisposition to obesity and cancer. While some members have phosphatase activity against the 3-phosphate of phosphoinositides, regulating the phosphorylation status of PtdIns3P and PtdIns(3,5)P2 implicated in membrane trafficking and autophagy, and producing PtdIns5P, others lack key residues in the catalytic site and are classified as dead-phosphatases...
September 15, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27658318/rab11-and-phosphoinositides-a-synergy-of-signal-transducers-in-the-control-of-vesicular-trafficking
#17
Carlo Cosimo Campa, Emilio Hirsch
Rab11 and phosphoinositides are signal transducers able to direct the delivery of membrane components to the cell surface. Rab11 is a small GTPase that, by cycling from an active to an inactive state, controls key events of vesicular transport, while phosphoinositides are major determinants of membrane identity, modulating compartmentalized small GTPase function. By sharing common effectors, these two signal transducers synergistically direct vesicular traffic to specific intracellular membranes. This review focuses on the latest advances regarding the mechanisms that ensure the compartmentalized regulation of Rab11 function through its interaction with phosphoinositides...
September 14, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/26776475/an-amyotrophic-lateral-sclerosis-linked-mutation-in-gle1-alters-the-cellular-pool-of-human-gle1-functional-isoforms
#18
Aditi, Laura Glass, T Renee Dawson, Susan R Wente
Amyotrophic lateral sclerosis (ALS) is a lethal late onset motor neuron disease with underlying cellular defects in RNA metabolism. In prior studies, two deleterious heterozygous mutations in the gene encoding human (h)Gle1 were identified in ALS patients. hGle1 is an mRNA processing modulator that requires inositol hexakisphosphate (IP6) binding for function. Interestingly, one hGLE1 mutation (c.1965-2A>C) results in a novel 88 amino acid C-terminal insertion, generating an altered protein. Like hGle1A, at steady state, the altered protein termed hGle1-IVS14-2A>C is absent from the nuclear envelope rim and localizes to the cytoplasm...
September 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/26639089/investigating-the-effect-of-arachidonate-supplementation-on-the-phosphoinositide-content-of-mcf10a-breast-epithelial-cells
#19
Karen E Anderson, Veronique Juvin, Jonathan Clark, Len R Stephens, Phillip T Hawkins
Phosphoinositides in primary mammalian tissue are highly enriched in a stearoyl/arachidonyl (C38:4) diacylgycerol backbone. However, mammalian cells grown in culture typically contain more diverse molecular species of phosphoinositides, characterised by a reduction in arachidonyl content in the sn-2 position. We have analysed the phosphoinositide species in MCF10a cells grown in culture by mass spectrometry. Under either serum or serum starved conditions the most abundant species of PI, PIP, PIP2 and PIP3 had masses which corresponded to C36:2, C38:4, C38:3, C38:2 and C36:1 diacylglycerol backbones and the relative proportions of each molecular species were broadly similar between each phosphoinositide class (approx...
September 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27639445/splicing-factor-gene-mutations-in-the-myelodysplastic-syndromes-impact-on-disease-phenotype-and-therapeutic-applications
#20
Andrea Pellagatti, Jacqueline Boultwood
Splicing factor gene mutations are the most frequent mutations found in patients with the myeloid malignancy myelodysplastic syndrome (MDS), suggesting that spliceosomal dysfunction plays a major role in disease pathogenesis. The aberrantly spliced target genes and deregulated cellular pathways associated with the commonly mutated splicing factor genes in MDS (SF3B1, SRSF2 and U2AF1) are being identified, illuminating the molecular mechanisms underlying MDS. Emerging data from mouse modeling studies indicate that the presence of splicing factor gene mutations can lead to bone marrow hematopoietic stem/myeloid progenitor cell expansion, impaired hematopoiesis and dysplastic differentiation that are hallmarks of MDS...
August 21, 2016: Advances in Biological Regulation
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