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What is the significance of canonical pathways

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https://www.readbyqxmd.com/read/27380180/x-ray-absorption-spectroscopic-characterization-of-the-diferric-peroxo-intermediate-of-human-deoxyhypusine-hydroxylase-in-the-presence-of-its-substrate-eif5a
#1
Andrew J Jasniewski, Lisa M Engstrom, Van V Vu, Myung Hee Park, Lawrence Que
Human deoxyhypusine hydroxylase (hDOHH) is an enzyme that is involved in the critical post-translational modification of the eukaryotic translation initiation factor 5A (eIF5A). Following the conversion of a lysine residue on eIF5A to deoxyhypusine (Dhp) by deoxyhypusine synthase, hDOHH hydroxylates Dhp to yield the unusual amino acid residue hypusine (Hpu), a modification that is essential for eIF5A to promote peptide synthesis at the ribosome, among other functions. Purification of hDOHH overexpressed in E...
September 2016: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/27194804/the-rate-and-spectrum-of-spontaneous-mutations-in-mycobacterium-smegmatis-a-bacterium-naturally-devoid-of-the-postreplicative-mismatch-repair-pathway
#2
Sibel Kucukyildirim, Hongan Long, Way Sung, Samuel F Miller, Thomas G Doak, Michael Lynch
Mycobacterium smegmatis is a bacterium that is naturally devoid of known postreplicative DNA mismatch repair (MMR) homologs, mutS and mutL, providing an opportunity to investigate how the mutation rate and spectrum has evolved in the absence of a highly conserved primary repair pathway. Mutation accumulation experiments of M. smegmatis yielded a base-substitution mutation rate of 5.27 × 10(-10) per site per generation, or 0.0036 per genome per generation, which is surprisingly similar to the mutation rate in MMR-functional unicellular organisms...
2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/26778749/lens-regeneration-from-the-cornea-requires-suppression-of-wnt-%C3%AE-catenin-signaling
#3
Paul W Hamilton, Yu Sun, Jonathan J Henry
The frog, Xenopus laevis, possesses a high capacity to regenerate various larval tissues, including the lens, which is capable of complete regeneration from the cornea epithelium. However, the molecular signaling mechanisms of cornea-lens regeneration are not fully understood. Previous work has implicated the involvement of the Wnt signaling pathway, but molecular studies have been very limited. Iris-derived lens regeneration in the newt (Wolffian lens regeneration) has shown a necessity for active Wnt signaling in order to regenerate a new lens...
April 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/26343727/non-canonical-hh-signaling-in-cancer-current-understanding-and-future-directions
#4
REVIEW
Dongsheng Gu, Jingwu Xie
As a major regulatory pathway for embryonic development and tissue patterning, hedgehog signaling is not active in most adult tissues, but is reactivated in a number of human cancer types. A major milestone in hedgehog signaling in cancer is the Food and Drug Administration (FDA) approval of a smoothened inhibitor Vismodegib for treatment of basal cell carcinomas. Vismodegib can block ligand-mediated hedgehog signaling, but numerous additional clinical trials have failed to show significant improvements in cancer patients...
2015: Cancers
https://www.readbyqxmd.com/read/26092120/tomoregulin-1-prevents-cardiac-hypertrophy-after-pressure-overload-in-mice-by-inhibiting-tak1-jnk-pathways
#5
Dan Bao, Dan Lu, Ning Liu, Wei Dong, Ying-Dong Lu, Chuan Qin, Lian-Feng Zhang
Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS) function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown...
August 1, 2015: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/25823927/aberrant-nuclear-factor-kappa-b-activity-in-acute-myeloid-leukemia-from-molecular-pathogenesis-to-therapeutic-target
#6
REVIEW
Jianbiao Zhou, Ying Qing Ching, Wee-Joo Chng
The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML...
March 20, 2015: Oncotarget
https://www.readbyqxmd.com/read/25636826/lps-stimulation-of-purified-human-platelets-is-partly-dependent-on-plasma-soluble-cd14-to-secrete-their-main-secreted-product-soluble-cd40-ligand
#7
Pauline Damien, Fabrice Cognasse, Marie-Ange Eyraud, Charles-Antoine Arthaud, Bruno Pozzetto, Olivier Garraud, Hind Hamzeh-Cognasse
BACKGROUND: Platelets are instrumental to primary haemostasis; in addition, as they are central to endothelium vascular repair, they play a role in physiological inflammation. Platelets have also been demonstrated to be key players in innate immunity and inflammation, expressing Toll-like receptors (TLRs) to sense microbial infection and initiate inflammatory responses. They are equipped to decipher distinct signals, to use alternate pathways of signalling through a complete signalosome, despite their lack of a nucleus, and to adjust the innate immune response appropriately for pathogens exhibiting different types of 'danger' signals...
2015: BMC Immunology
https://www.readbyqxmd.com/read/25625619/minireview-tipping-the-balance-ligand-independent-activation-of-steroid-receptors
#8
Marcela A Bennesch, Didier Picard
Steroid receptors are prototypical ligand-dependent transcription factors and a textbook example for allosteric regulation. According to this canonical model, binding of cognate steroid is an absolute requirement for transcriptional activation. Remarkably, the simple one ligand-one receptor model could not be farther from the truth. Steroid receptors, notably the sex steroid receptors, can receive multiple inputs. Activation of steroid receptors by other signals, working through their own signaling pathways, in the absence of the cognate steroids, represents the most extreme form of signaling cross talk...
March 2015: Molecular Endocrinology
https://www.readbyqxmd.com/read/25046115/bag3-induces-the-sequestration-of-proteasomal-clients-into-cytoplasmic-puncta-implications-for-a-proteasome-to-autophagy-switch
#9
Melania Minoia, Alessandra Boncoraglio, Jonathan Vinet, Federica F Morelli, Jeanette F Brunsting, Angelo Poletti, Sabine Krom, Eric Reits, Harm H Kampinga, Serena Carra
Eukaryotic cells use autophagy and the ubiquitin-proteasome system as their major protein degradation pathways. Upon proteasomal impairment, cells switch to autophagy to ensure proper clearance of clients (the proteasome-to-autophagy switch). The HSPA8 and HSPA1A cochaperone BAG3 has been suggested to be involved in this switch. However, at present it is still unknown whether and to what extent BAG3 can indeed reroute proteasomal clients to the autophagosomal pathway. Here, we show that BAG3 induces the sequestration of ubiquitinated clients into cytoplasmic puncta colabeled with canonical autophagy linkers and markers...
September 2014: Autophagy
https://www.readbyqxmd.com/read/24887235/ligand-independent-canonical-wnt-activity-in-canine-mammary-tumor-cell-lines-associated-with-aberrant-lef1-expression
#10
Ana Gracanin, Elpetra P M Timmermans-Sprang, Monique E van Wolferen, Nagesha A S Rao, Juraj Grizelj, Silvijo Vince, Eva Hellmen, Jan A Mol
Pet dogs very frequently develop spontaneous mammary tumors and have been suggested as a good model organism for breast cancer research. In order to obtain an insight into underlying signaling mechanisms during canine mammary tumorigenesis, in this study we assessed the incidence and the mechanism of canonical Wnt activation in a panel of 12 canine mammary tumor cell lines. We show that a subset of canine mammary cell lines exhibit a moderate canonical Wnt activity that is dependent on Wnt ligands, similar to what has been described in human breast cancer cell lines...
2014: PloS One
https://www.readbyqxmd.com/read/24618541/interaction-between-bone-morphogenetic-protein-receptor-type-2-and-estrogenic-compounds-in-pulmonary-arterial-hypertension
#11
Joshua P Fessel, Xinping Chen, Andrea Frump, Santhi Gladson, Tom Blackwell, Christie Kang, Jennifer Johnson, James E Loyd, Anna Hemnes, Eric Austin, James West
Abstract The majority of heritable pulmonary arterial hypertension (HPAH) cases are associated with mutations in bone morphogenetic protein receptor type 2 (BMPR2). BMPR2 mutation carries about a 20% lifetime risk of PAH development, but penetrance is approximately three times higher in females. Previous studies have shown a correlation between estrogen metabolism and penetrance, with increased levels of the estrogen metabolite 16α-hydroxyestrone (16αOHE) and reduced levels of the metabolite 2-methoxyestrogen (2ME) associated with increased risk of disease...
September 2013: Pulmonary Circulation
https://www.readbyqxmd.com/read/23876795/combined-cpg-and-poly-i-c-stimulation-of-monocytes-results-in-unique-signaling-activation-not-observed-with-the-individual-ligands
#12
Ryan J Arsenault, Michael H Kogut, Haiqi He
Toll-like receptors (TLRs) bind to components of microbes, activate cellular signal transduction pathways and stimulate innate immune responses. Previously, we have shown in chicken monocytes that the combination of CpG, the ligand for TLR21 (the chicken equivalent of TLR9), and poly I:C, the ligand for TLR3, results in a synergistic immune response. In order to further characterize this synergy, kinome analysis was performed on chicken monocytes stimulated with either unmethylated CpG oligodeoxynucleotides (CpG) and polyinosinic-polycytidylic acid (poly I:C) individually or in combination for either 1h or 4h...
November 2013: Cellular Signalling
https://www.readbyqxmd.com/read/23763941/mitochondrial-metabolism-of-sexual-and-asexual-blood-stages-of-the-malaria-parasite-plasmodium-falciparum
#13
James I MacRae, Matthew Wa Dixon, Megan K Dearnley, Hwa H Chua, Jennifer M Chambers, Shannon Kenny, Iveta Bottova, Leann Tilley, Malcolm J McConville
BACKGROUND: The carbon metabolism of the blood stages of Plasmodium falciparum, comprising rapidly dividing asexual stages and non-dividing gametocytes, is thought to be highly streamlined, with glycolysis providing most of the cellular ATP. However, these parasitic stages express all the enzymes needed for a canonical mitochondrial tricarboxylic acid (TCA) cycle, and it was recently proposed that they may catabolize glutamine via an atypical branched TCA cycle. Whether these stages catabolize glucose in the TCA cycle and what is the functional significance of mitochondrial metabolism remains unresolved...
2013: BMC Biology
https://www.readbyqxmd.com/read/23416978/wnt7b-mediates-autocrine-wnt-%C3%AE-catenin-signaling-and-anchorage-independent-growth-in-pancreatic-adenocarcinoma
#14
M D Arensman, A N Kovochich, R M Kulikauskas, A R Lay, P-T Yang, X Li, T Donahue, M B Major, R T Moon, A J Chien, D W Dawson
Developmental and cancer models show Wnt/β-catenin-dependent signaling mediates diverse phenotypic outcomes in the pancreas that are dictated by context, duration and strength of activation. While generally assumed to be pro-tumorigenic, it is unclear to what extent dysregulation of Wnt/β-catenin signaling impacts tumor progression in pancreatic adenocarcinoma (PDAC). In the present study, Wnt/β-catenin activity was characterized across a spectrum of PDAC cell lines and primary tumors. Reporter and gene expression-based assays revealed wide heterogeneity in Wnt/β-catenin transcriptional activity across PDAC cell lines and patient tumors, as well as variable responsiveness to exogenous Wnt ligand stimulation...
February 13, 2014: Oncogene
https://www.readbyqxmd.com/read/23139211/smad2-smad3-and-smad4-mutations-in-colorectal-cancer
#15
Nicholas I Fleming, Robert N Jorissen, Dmitri Mouradov, Michael Christie, Anuratha Sakthianandeswaren, Michelle Palmieri, Fiona Day, Shan Li, Cary Tsui, Lara Lipton, Jayesh Desai, Ian T Jones, Stephen McLaughlin, Robyn L Ward, Nicholas J Hawkins, Andrew R Ruszkiewicz, James Moore, Hong-Jian Zhu, John M Mariadason, Antony W Burgess, Dana Busam, Qi Zhao, Robert L Strausberg, Peter Gibbs, Oliver M Sieber
Activation of the canonical TGF-β signaling pathway provides growth inhibitory signals in the normal intestinal epithelium. Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear. A cohort of 744 primary CRCs and 36 CRC cell lines were sequenced for SMAD4, SMAD2, and SMAD3 and analyzed for allelic loss by single-nucleotide polymorphism (SNP) microarray analysis. Mutation spectra were compared between the genes, the pathogenicity of mutations was assessed, and relationships with clinicopathologic features were examined...
January 15, 2013: Cancer Research
https://www.readbyqxmd.com/read/22692208/activation-of-transient-receptor-potential-canonical-3-trpc3-mediated-ca2-entry-by-a1-adenosine-receptor-in-cardiomyocytes-disturbs-atrioventricular-conduction
#16
Jessica Sabourin, Fabrice Antigny, Elodie Robin, Maud Frieden, Eric Raddatz
Although the activation of the A(1)-subtype of the adenosine receptors (A(1)AR) is arrhythmogenic in the developing heart, little is known about the underlying downstream mechanisms. The aim of this study was to determine to what extent the transient receptor potential canonical (TRPC) channel 3, functioning as receptor-operated channel (ROC), contributes to the A(1)AR-induced conduction disturbances. Using embryonic atrial and ventricular myocytes obtained from 4-day-old chick embryos, we found that the specific activation of A(1)AR by CCPA induced sarcolemmal Ca(2+) entry...
August 3, 2012: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/22572954/pml-body-meets-telomere-the-beginning-of-an-alternate-ending
#17
REVIEW
Inn Chung, Sarah Osterwald, Katharina I Deeg, Karsten Rippe
The unlimited proliferation potential of cancer cells requires the maintenance of their telomeres. This is frequently accomplished by reactivation of telomerase. However, in a significant fraction of tumors an alternative lengthening of telomeres (ALT) mechanism is active. The molecular mechanism of the ALT pathway remains elusive. In particular, the role of characteristic complexes of promyelocytic leukemia nuclear bodies (PML-NBs) with telomeres, the ALT-associated PML-NBs (APBs), is currently under investigation...
May 2012: Nucleus
https://www.readbyqxmd.com/read/22489561/wnt2-locus-is-involved-in-genetic-susceptibility-of-peyronie-s-disease
#18
Guido H Dolmans, Paul M Werker, Igle J de Jong, Rien J Nijman, Cisca Wijmenga, Roel A Ophoff
INTRODUCTION: Peyronie's disease (PD) is a fibromatosis of the penis, with a pathology very similar to what is seen in the hand (palmar fascia) in Dupuytren's disease (DD). Recently, we performed a genome-wide association study and identified nine genetic loci containing common variants associated with DD. Seven of these loci mapped within or near genes of the canonical WNT pathway and each locus yielded relatively large odds ratios (ORs) for DD disease status. AIM: Given the clinical overlap between PD and DD, we examined whether the nine DD susceptibility loci are also involved in PD...
May 2012: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/20198150/intracortical-cartography-in-an-agranular-area
#19
Gordon M G Shepherd
A well-defined granular layer 4 is a defining cytoarchitectonic feature associated with sensory areas of mammalian cerebral cortex, and one with hodological significance: the local axons ascending from cells in thalamorecipient layer 4 and connecting to layer 2/3 pyramidal neurons form a major feedforward excitatory interlaminar projection. Conversely, agranular cortical areas, lacking a distinct layer 4, pose a hodological conundrum: without a laminar basis for the canonical layer 4-->2/3 pathway, what is the basic circuit organization? This review highlights current challenges and prospects for local-circuit electroanatomy and electrophysiology in agranular cortex, focusing on the mouse...
2009: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/17705789/oxygen-sensing-and-hypoxia-induced-responses
#20
REVIEW
Mathew L Coleman, Peter J Ratcliffe
Low cellular oxygenation (hypoxia) represents a significant threat to the viability of affected tissues. Multicellular organisms have evolved a highly conserved signalling pathway that directs many of the changes in gene expression that underpin physiological oxygen homoeostasis. Oxygen-sensing enzymes in this pathway control the activity of the HIF (hypoxia-inducible factor) transcription factor by the direct incorporation of molecular oxygen into the post-translational hydroxylation of specific residues. This represents the canonical hypoxia signalling pathway which regulates a plethora of genes involved in adaptation to hypoxia...
2007: Essays in Biochemistry
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