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Advances in Biological Regulation

Reyna Murry, Olaf Kniemeyer, Katrin Krause, Adolfo Saiardi, Erika Kothe
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. In this study, a crosstalk between Ras signaling and inositol phosphate signaling by inositol monophosphatase (IMPase) is revealed. Constitutively active Ras1 leads to the repression of IMPase transcription and lithium action on IMPase activity is compensated by the induction of IMPase at transcriptome level...
January 3, 2019: Advances in Biological Regulation
Yuri Pekarsky, Carlo M Croce
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. A corollary of this is that CLL is very sensitive to the anti BCL2 drug venetoclax that can induce complete remission in CLL patients. Since leukemia patients may carry billions of leukemia cells, it is quite likely that some (few) of the leukemic cells are resistant to venetoclax...
December 13, 2018: Advances in Biological Regulation
María José Hernández-Corbacho, Lina M Obeid
No abstract text is available yet for this article.
December 13, 2018: Advances in Biological Regulation
Elizabeth Michele Davies, Rajendra Gurung, Kai Qin Le, Christina Anne Mitchell
Phosphoinositide signaling regulates numerous downstream effectors that mediate cellular processes which influence cell cycle progression, migration, proliferation, growth, survival, metabolism and vesicular trafficking. A prominent role for phosphoinositide 3-kinase, which generates phosphatidylinositol 3,4,5-trisphosphate, a phospholipid that activates a plethora of effectors including AKT and FOXO during embryonic and postnatal angiogenesis, has been described. In addition, phosphatidylinositol 3-phosphate signaling is required for endosomal trafficking, which contributes to vascular remodeling...
November 26, 2018: Advances in Biological Regulation
Binks W Wattenberg
The myelin sheath, produced by oligodendrocytes in the central nervous system, provides essential electrical insulation to neurons, but also is critical for viability of neurons. Both the protein and lipid composition of this fascinating membrane is unique. Here the focus is on the sphingolipids that are highly abundant in myelin and, in particular, how they are produced. This review discusses how sphingolipid metabolism is regulated. In particular the subcellular localization of lipid metabolic enzymes is discussed and how inter-organelle transport can affect the metabolic routes that sphingolipid precursors take...
November 23, 2018: Advances in Biological Regulation
Johana M Lambert, Andrea K Anderson, L Ashley Cowart
Adipose tissue lies at the heart of obesity, mediating its many effects upon the rest of the body, with its unique capacity to expand and regenerate, throughout the lifespan of the organism. Adipose is appreciated as an endocrine organ, with its myriad adipokines that elicit both physiological and pathological outcomes. Sphingolipids, bioactive signaling molecules, affect many aspects of obesity and the metabolic syndrome. While sphingolipids are appreciated in the context of these diseases in other tissues, there are many discoveries yet to be uncovered in the adipose tissue...
December 2018: Advances in Biological Regulation
Mariana Nikolova-Karakashian
Sphingolipids are class of metabolically distinct lipids that play structural and signaling functions in all organisms. Sphingolipid metabolism is deregulated during various diseases such as cancer, neurological and immune disorders, and metabolic syndrome. With the advancement of sphingo-lipidomics and sphingo-genomics, an understanding of the specific roles of ceramide, the quintessential bioactive sphingolipid, in fatty liver disease has taken shape. Two major pathways for ceramide generation, the de novo pathway and the sphingomyelinase pathway are activated in the course of both, the non-alcoholic and the alcoholic, forms of fatty liver disease...
December 2018: Advances in Biological Regulation
Tess V Dupre, Leah J Siskind
Acute kidney injury (AKI) is most simply defined as the rapid loss of kidney function in a matter of hours to days. AKI can manifest in a number of ways including pre-renal, post-renal, or intrinsic AKI. During acute kidney injury, multiple pathogenic processes are activated including inflammation, cell death, and the generation of reactive oxygen species, just to name a few. Sphingolipids are known to play a role in a number of the pathogenic pathways involved in the pathogenesis of many types of AKI, which suggests a role for sphingolipids in AKI...
December 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...
December 2018: Advances in Biological Regulation
Deanna Davis, Muthukumar Kannan, Binks Wattenberg
Sphingolipids comprise a diverse family of lipids that perform multiple functions in both structure of cellular membranes and intra- and inter-cellular signaling. The diversity of this family is generated by an array of enzymes that produce individual classes and molecular species of family members and enzymes which catabolize those lipids for recycling pathways. However, all of these lipids begin their lives with a single step, the condensation of an amino acid, almost always serine, and a fatty acyl-CoA, almost always the 16-carbon, saturated fatty acid, palmitate...
December 2018: Advances in Biological Regulation
Jennifer O'Sullivan, Adam J Mead
Myeloproliferative neoplasms (MPNs) are haematopoietic stem cell-derived clonal disorders characterised by proliferation of some or all myeloid lineages, depending on the subtype. MPNs are classically categorized into three disease subgroups; essential thrombocythaemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF). The majority (>85%) of patients carry a disease-initiating or driver mutation, the most prevalent occurring in the janus kinase 2 gene (JAK2 V617F), followed by calreticulin (CALR) and myeloproliferative leukaemia virus (MPL) genes...
November 22, 2018: Advances in Biological Regulation
Jie Liang, Gertrud Maria Hänsch, Katrin Hübner, Yvonne Samstag
Sulforaphane (SFN) is a naturally occurring isothiocyanate derived from cruciferous vegetables such as broccoli. It has been reported to inhibit the growth of a variety of cancers, such as breast, prostate, colon, skin, lung, gastric or bladder cancer. SFN is supposed to act primarily as an antioxidant due to the activation of the Nrf2-Keap1 signaling pathway. This enhances the activity of phase II detoxifying enzymes and the trapping of free radicals. Finally, SFN induces cell cycle arrest or apoptosis of tumor cells...
November 22, 2018: Advances in Biological Regulation
Binks W Wattenberg, Sarah Spiegel
No abstract text is available yet for this article.
November 14, 2018: 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
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