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Advances in Biological Regulation

Giulia Ramazzotti, Roberta Fiume, Francesca Chiarini, Gabriele Campana, Stefano Ratti, Anna Maria Billi, Lucia Manzoli, Matilde Y Follo, Pann-Gill Suh, James McCubrey, Lucio Cocco, Irene Faenza
Adipose-derived stem cells (ADSCs) are multipotent mesenchymal stem cells that have the ability to differentiate into several cell types, including chondrocytes, osteoblasts, adipocytes, and neural cells. Given their easy accessibility and abundance, they became an attractive source of mesenchymal stem cells, as well as candidates for developing new treatments for reconstructive medicine and tissue engineering. Our study identifies a new signaling pathway that promotes ADSCs osteogenic differentiation and links the lipid signaling enzyme phospholipase C (PLC)-β1 to the expression of the cell cycle protein cyclin E...
November 5, 2018: Advances in Biological Regulation
Stephen B Shears, Huanchen Wang
The protein kinase family is characterized by substantial conservation of architectural elements that are required for both ATP binding and phosphotransferase activity. Many of these structural features have also been identified in homologous enzymes that phosphorylate a variety of alternative, non-protein substrates. A comparative structural analysis of these different kinase sub-classes is a portal to a greater understanding of reaction mechanisms, enzyme regulation, inhibitor-development strategies, and superfamily-level evolutionary relationships...
October 27, 2018: Advances in Biological Regulation
Nicolas Coant, Yusuf A Hannun
Extensive research conducted in the last three decades has identified the roles for the main bioactive sphingolipids, namely ceramide, sphingosine, and sphingosine 1-phosphate (S1P) as key regulators of cellular homeostasis, growth and death. One of the major groups of enzymes in the ceramide pathway, ceramidases, converts ceramide into sphingosine and fatty acids, with sphingosine being further metabolized to S1P. Thus, these enzymes play important roles in the network controlling the functions associated with these bioactive sphingolipids...
October 26, 2018: Advances in Biological Regulation
Laura Goins, Stefka Spassieva
Sphingoid bases (also known as long-chain bases) form the backbone of sphingolipids. Sphingolipids comprise a large group of lipid molecules, which function as the building blocks of biological membranes and play important signaling and regulatory roles within cells. The roles of sphingoid bases in neurotoxicity and neurodegeneration have yet to be fully elucidated, as they are complex and multi-faceted. This comprises a new frontier of research that may provide us with important clues regarding their involvement in neurological health and disease...
October 23, 2018: Advances in Biological Regulation
Stephen L Abrams, Matilde Y Follo, Linda S Steelman, Kvin Lertpiriyapong, Lucio Cocco, Stefano Ratti, Alberto M Martelli, Saverio Candido, Massimo Libra, Ramiro M Murata, Pedro L Rosalen, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Weifeng Mao, Paolo Lombardi, James A McCubrey
Berberine (BBR) is a common nutraceutical consumed by millions worldwide. BBR has many different effects on human health, e.g., diabetes, diarrhea, inflammation and now more recently it has been proposed to have potent anti-cancer effects. BBR has been shown to suppress the growth of cancer cells more than normal cells. BBR has been proposed to exert its growth-inhibitory effects by many different biochemical mechanisms including: suppression of cell cycle progression, induction of reactive oxygen species, induction of apoptosis and autophagy and interactions with DNA potentially leading to DNA damage, and altered gene expression...
October 17, 2018: Advances in Biological Regulation
Hamid Dolatshad, Dharamveer Tatwavedi, Doaa Ahmed, Jana F Tegethoff, Jacqueline Boultwood, Andrea Pellagatti
Induced pluripotent stem cells (iPSCs) were first described over a decade ago and are currently used in various basic biology and clinical research fields. Recent advances in the field of human iPSCs have opened the way to a better understanding of the biology of human diseases. Disease-specific iPSCs provide an unparalleled opportunity to establish novel human cell-based disease models, with the potential to enhance our understanding of the molecular mechanisms underlying human malignancies, and to accelerate the identification of effective new drugs...
October 10, 2018: Advances in Biological Regulation
Qianqian Ma, Sandra B Gabelli, Daniel M Raben
Lipid kinases regulate a wide variety of cellular functions and have emerged as one the most promising targets for drug design. Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PtdOH). Despite the critical role in lipid biosynthesis, both DAG and PtdOH have been shown as bioactive lipids mediating a number of signaling pathways. Although there is increasing recognition of their role in signaling systems, our understanding of the key enzyme which regulate the balance of these two lipid messages remain limited...
September 28, 2018: Advances in Biological Regulation
Youn-Jeong Choi, Julie D Saba
Sphingosine-1-phosphate lyase (SPL) is an intracellular enzyme that controls the final step in the sphingolipid degradative pathway, the only biochemical pathway for removal of sphingolipids. Specifically, SPL catalyzes the cleavage of sphingosine 1-phosphate (S1P) at the C2-3 carbon bond, resulting in its irreversible degradation to phosphoethanolamine (PE) and hexadecenal. The substrate of the reaction, S1P, is a bioactive sphingolipid metabolite that signals through a family of five G protein-coupled S1P receptors (S1PRs) to mediate biological activities including cell migration, cell survival/death/proliferation and cell extrusion, thereby contributing to development, physiological functions and - when improperly regulated - the pathophysiology of disease...
September 25, 2018: Advances in Biological Regulation
Hyeon-Jeong Hwang, Hyun-Jun Jang, Lucio Cocco, Pann-Ghill Suh
Phospholipase Cβ (PLCβ) is a membrane-associated enzyme activated by membrane receptors, especially G-protein coupled receptors (GPCRs). It propagates intracellular signaling by mediating phospholipid metabolism and generating key second messengers, such as inositol triphosphate and diacylglycerol, leading to intracellular Ca2+ mobilization and activation of kinases, such as protein kinases C. In pancreatic β-cells, PLCβ-mediated signaling activated by various factors, such as free fatty acids and neuronal and hormonal ligands, has been confirmed as being involved in the regulation of insulin secretion, and PLCβs have been regarded as essential mediators for augmenting insulin secretion...
September 23, 2018: Advances in Biological Regulation
Guanghu Wang, Erhard Bieberich
For many decades, research on sphingolipids associated with neurodegenerative disease focused on alterations in glycosphingolipids, particularly glycosylceramides (cerebrosides), sulfatides, and gangliosides. This seemed quite natural since many of these glycolipids are constituents of myelin and accumulated in lipid storage diseases (sphingolipidoses) resulting from enzyme deficiencies in glycolipid metabolism. With the advent of recognizing ceramide and its derivative, sphingosine-1-phosphate (S1P), as key players in lipid cell signaling and regulation of cell death and survival, research focus shifted toward these two sphingolipids...
September 22, 2018: Advances in Biological Regulation
Mariana L Oliveira, Padma Akkapeddi, Daniel Ribeiro, Alice Melão, João T Barata
Interleukin 7 (IL-7) and its receptor (IL-7R, a heterodimer of IL-7Rα and γc) are essential for normal lymphoid development. In their absence, severe combined immunodeficiency occurs. By contrast, excessive IL-7/IL-7R-mediated signaling can drive lymphoid leukemia development, disease acceleration and resistance to chemotherapy. IL-7 and IL-7R activate three main pathways: STAT5, PI3K/Akt/mTOR and MEK/Erk, ultimately leading to the promotion of leukemia cell viability, cell cycle progression and growth. However, the contribution of each of these pathways towards particular functional outcomes is still not completely known and appears to differ between normal and malignant states...
September 19, 2018: Advances in Biological Regulation
Laura Glass, Susan R Wente
Stress granules (SGs) are non-membrane bound organelles that form in response to multiple different stress stimuli, including exposure to sodium arsenite. SGs are postulated to support cells during periods of stress and provide a protective effect, allowing survival. Gle1 is a highly conserved, essential modulator of RNA-dependent DEAD-box proteins that exists as at least two distinct isoforms in human cells. Gle1A is required for proper SG formation, whereas Gle1B functions in mRNA export at the nuclear pore complex...
September 18, 2018: Advances in Biological Regulation
Martin Sztacho, Margarita Sobol, Can Balaban, Sara Eliana Escudeiro Lopes, Pavel Hozák
Nuclear phosphoinositides are recognized as regulators of many nuclear processes including chromatin remodeling, splicing, transcription, DNA repair and epigenetics. These processes are spatially organized in different nuclear compartments. Phase separation is involved in the formation of various nuclear compartments and molecular condensates separated from surrounding environment. The surface of such structures spatiotemporally coordinates formation of protein complexes. PI(4,5)P2 (PIP2) integration into phase-separated structures might provide an additional step in their spatial diversification by attracting certain proteins with affinity to PIP2...
September 17, 2018: Advances in Biological Regulation
Ifeoluwa Adewumi, Camila López, James R Davie
The mitogen- and stress-activated protein kinases activated by the extracellular-signal-regulated kinase 1/2 and/or stress-activated protein kinase 2/p38 mitogen-activated protein kinase pathways are recruited to the regulatory region of a subset of genes termed immediate-early genes, often leading to their induction. These genes, many of which code for transcription factors, have been directly linked to the phenotypic events in carcinogenesis. In this paper, we focus on the mitogen- and stress-activated protein kinases; their discovery, activation, H3 phosphorylation and recent discoveries in their roles in cancer...
September 17, 2018: Advances in Biological Regulation
Gabor J Tigyi, Junming Yue, Derek D Norman, Erzsebet Szabo, Andrea Balogh, Louisa Balazs, Guannan Zhao, Sue Chin Lee
The lipid mediator lysophosphatidic acid (LPA) in biological fluids is primarily produced by cleavage of lysophospholipids by the lysophospholipase D enzyme Autotaxin (ATX). LPA has been identified and abundantly detected in the culture medium of various cancer cell types, tumor effusates, and ascites fluid of cancer patients. Our current understanding of the physiological role of LPA established its role in fundamental biological responses that include cell proliferation, metabolism, neuronal differentiation, angiogenesis, cell migration, hematopoiesis, inflammation, immunity, wound healing, regulation of cell excitability, and the promotion of cell survival by protecting against apoptotic death...
September 16, 2018: Advances in Biological Regulation
Hervé Moine, Nicolas Vitale
Fine-tuned regulation of new proteins synthesis is key to the fast adaptation of cells to their changing environment and their response to external cues. Protein synthesis regulation is particularly refined and important in the case of highly polarized cells like neurons where translation occurs in the subcellular dendritic compartment to produce long-lasting changes that enable the formation, strengthening and weakening of inter-neuronal connection, constituting synaptic plasticity. The changes in local synaptic proteome of neurons underlie several aspects of synaptic plasticity and new protein synthesis is necessary for long-term memory formation...
September 15, 2018: Advances in Biological Regulation
Yoshiteru Kagawa, Banlanjo A Umaru, Islam Ariful, Subrata Kumar Shil, Hirofumi Miyazaki, Yui Yamamoto, Masaki Ogata, Yuji Owada
Lipids are major molecules for the function of organisms and are involved in the pathophysiology of various diseases. Fatty acids (FAs) signaling and their metabolism are some of the most important pathways in tumor development, as lipids serve as energetic sources during carcinogenesis. Fatty acid binding proteins (FABPs) facilitate FAs transport to different cell organelles, modulating their metabolism along with mediating other physiological activities. FABP7, brain-typed FABP, is thought to be an important molecule for cell proliferation in healthy as well as diseased organisms...
September 15, 2018: Advances in Biological Regulation
Peter P Ruvolo
The microenvironment within the bone marrow (BM) contains support cells that promote leukemia cell survival and suppress host anti-tumor defenses. Galectins are a family of beta-galactoside binding proteins that are critical components in the tumor microenvironment. Galectin 1 (LGALS1) and Galectin 3 (LGALS3) as regulators of RAS signaling intracellularly and as inhibitors of immune cells extracellularly are perhaps the best studied members for their role in leukemia biology. Interest in Galectin 9 (LGALS9) is growing as this galectin has been identified as an immune checkpoint molecule...
September 12, 2018: Advances in Biological Regulation
Caitlyn E Bowman, Michael J Wolfgang
Malonyl-CoA is a central metabolite in fatty acid biochemistry. It is the rate-determining intermediate in fatty acid synthesis but is also an allosteric inhibitor of the rate-setting step in mitochondrial long-chain fatty acid oxidation. While these canonical cytoplasmic roles of malonyl-CoA have been well described, malonyl-CoA can also be generated within the mitochondrial matrix by an alternative pathway: the ATP-dependent ligation of malonate to Coenzyme A by the malonyl-CoA synthetase ACSF3. Malonate, a competitive inhibitor of succinate dehydrogenase of the TCA cycle, is a potent inhibitor of mitochondrial respiration...
September 5, 2018: Advances in Biological Regulation
Jamie L Sturgill
Asthma is defined as a chronic inflammatory condition in the lung and is characterized by episodic shortness of breath with expiratory wheezing and cough. Asthma is a serious public health concern globally with an estimated incidence over 300 million. Asthma is a complex disease in that it manifests as disease of gene and environmental interactions. Sphingolipids are a unique class of lipids involved in a host of biological functions ranging from serving as key cellular membrane lipids to acting as critical signaling molecules...
September 5, 2018: Advances in Biological Regulation
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