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https://www.readbyqxmd.com/read/28620760/notch-an-interactive-player-in-neurogenesis-and-disease
#1
REVIEW
Runrui Zhang, Anna Engler, Verdon Taylor
Notch signaling is evolutionarily conserved from Drosophila to human. It plays critical roles in neural stem cell maintenance and neurogenesis in the embryonic brain as well as in the adult brain. Notch functions greatly depend on careful regulation and cross-talk with other regulatory mechanisms. Deregulation of Notch signaling is involved in many neurodegenerative diseases and brain disorders. Here, we summarize the fundamental role of Notch in neuronal development and specification and discuss how epigenetic regulation and pathway cross-talk contribute to Notch function...
June 15, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28620086/a-genetic-screen-reveals-an-unexpected-role-for-yorkie-signaling-in-jak-stat-dependent-hematopoietic-malignancies-in-drosophila-melanogaster
#2
Abigail M Anderson, Alessandro A Bailetti, Elizabeth Rodkin, Atish De, Erika A Bach
A gain-of-function mutation in the tyrosine kinase JAK2 (JAK2(V617F) ) causes human myeloproliferative neoplasms (MPNs). These patients present with high numbers of myeloid lineage cells and have numerous complications. Since current MPN therapies are not curative, there is a need to find new regulators and targets of JAK/STAT signaling that may represent additional clinical interventions. Drosophila melanogaster offers a low complexity model to study MPNs as JAK/STAT signaling is simplified with only one JAK (Hopscotch (Hop)) and one STAT (Stat92E)...
June 15, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28619822/cop9-signalosome-subunits-protect-capicua-from-map-kinase-dependent-and-independent-mechanisms-of-degradation
#3
Annabelle Suisse, DanQing He, Kevin Legent, Jessica E Treisman
The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here we show that mutations in the Drosophila COP9 signalosome subunit 1b (CSN1b) gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of CSN1b mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes. It does so by protecting Capicua, a transcriptional repressor of EGFR target genes, from EGFR pathway-dependent ubiquitination by a Cullin 1/SKP1-related A/Archipelago E3 ligase and subsequent proteasomal degradation...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28619817/canoe-and-scribble-loss-synergizes-causing-tumor-like-overgrowth-via-ras-activation-in-neural-stem-cells-and-epithelia
#4
Noemí Rives-Quinto, Maribel Franco, Ana de Torres-Jurado, Ana Carmena
Over the past decade an intriguing connection between asymmetric cell division, stem cells and tumorigenesis has emerged. Neuroblasts, the neural stem cells of the Drosophila central nervous system, divide asymmetrically and constitute an excellent paradigm for further investigating that connection. Here we show that the simultaneous loss of the asymmetric cell division regulators Canoe (Afadin in mammals) and Scribble in neuroblast clones leads to tumor-like overgrowth through both a severe disruption of the asymmetric cell division process and a canoe loss-mediated Ras-PI3K-Akt activation...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28600967/mechanisms-of-cell-competition-emerging-from-drosophila-studies
#5
Nicholas E Baker
Cell competition was described in Drosophila as the loss from mosaic tissues of otherwise viable cells heterozygous for Ribosomal protein mutations ('Minutes'). Cell competition has now been described to occur between multiple other genotypes, such as cells differing in myc expression levels, or mutated for neoplastic tumor suppressors. Recent studies implicate innate immunity components, and possibly mechanical stress, compression and cell intercalation as a consequence of differential growth rates in competitive cell death...
June 7, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28583847/timeless-confers-cisplatin-resistance-in-nasopharyngeal-carcinoma-by-activating-the-wnt-%C3%AE-catenin-signaling-pathway-and-promoting-the-epithelial-mesenchymal-transition
#6
Sai-Lan Liu, Huan-Xin Lin, Chu-Yong Lin, Xiao-Qing Sun, Li-Ping Ye, Fang Qiu, Wen Wen, Xin Hua, Xian-Qiu Wu, Jun Li, Li-Bing Song, Ling Guo
This study investigated the expression, clinicopathological significance and mechanism of action of TIMELESS, a mammalian homolog of a Drosophila circadian rhythm gene, in nasopharyngeal carcinoma. Quantitative real-time PCR, western blotting and immunohistochemistry revealed TIMELESS was upregulated in NPC cell lines (n = 8 vs. NP69 cells), and freshly-frozen (n = 6) and paraffin-embedded human NPC specimens (n = 108 vs. normal samples/non-tumor cells). TIMELESS expression was associated with T category (P = 0...
June 3, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28574763/the-dark-side-of-hippo-signaling-a-cancer-promoter-role
#7
Brandon Dunn, Xianjue Ma
The Hippo signaling pathway regulates organ size and tissue homeostasis. Given this role it is unsurprising that dysregulation of this pathway has implications for cancer progression. A convincing body of literature shows that the Hippo pathway serves a tumor suppressive function with its inactivation leading to massive overgrowth. However, additional studies have also shown that activation of Hippo signaling can promote tumor progression. It remains unknown how a single pathway can produce such diametrically opposed effects...
June 2, 2017: Fly
https://www.readbyqxmd.com/read/28571774/modulatory-effects-of-metformin-on-mutagenicity-and-epithelial-tumor-incidence-in-doxorubicin-treated-drosophila-melanogaster
#8
Victor Constante Oliveira, Sarah Alves Rodrigues Constante, Priscila Capelari Orsolin, Júlio César Nepomuceno, Alexandre Azenha Alves de Rezende, Mário Antônio Spanó
Metformin (MET) is an anti-diabetic drug used to prevent hepatic glucose release and increase tissue insulin sensitivity. Diabetic cancer patients are on additional therapy with anticancer drugs. Doxorubicin (DXR) is a cancer chemotherapeutic agent that interferes with the topoisomerase II enzyme and generates free radicals. MET (2.5, 5, 10, 25 or 50 mM) alone was examined for mutagenicity, recombinogenicity and carcinogenicity, and combined with DXR (0.4 mM) for antimutagenicity, antirecombinogenicity and anticarcinogenicity, using the Somatic Mutation and Recombination Test and the Test for Detecting Epithelial Tumor Clones in Drosophila melanogaster...
May 29, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28566755/merlin-is-required-for-coordinating-proliferation-of-two-stem-cell-lineages-in-the-drosophila-testis
#9
Mayu Inaba, Dorothy R Sorenson, Matt Kortus, Viktoria Salzmann, Yukiko M Yamashita
Although the mechanisms that balance self-renewal and differentiation of a stem cell lineage have been extensively studied, it remains poorly understood how tissues that contain multiple stem cell lineages maintain balanced proliferation among distinct lineages: when stem cells of a particular lineage proliferate, how do the other lineages respond to maintain the correct ratio of cells among linages? Here, we show that Merlin (Mer), a homolog of the human tumor suppressor neurofibromatosis 2, is required to coordinate proliferation of germline stem cells (GSCs) and somatic cyst stem cells (CySCs) in the Drosophila testis...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28552546/use-of-the-crispr-cas9-system-for-genome-editing-in-cultured-drosophila-ovarian-somatic-cells
#10
Hirotsugu Ishizu, Tetsutaro Sumiyoshi, Mikiko C Siomi
The CRISPR-Cas9 system can be used for genome engineering in many organisms. PIWI-interacting RNAs (piRNAs) play a crucial role in repressing transposons to maintain genome integrity in Drosophila ovaries, and cultured ovarian somatic cells (OSCs) are widely used to elucidate the molecular mechanisms underlying the piRNA pathway. However, the germline-specific piRNA amplification system known as the ping-pong machinery does not occur in OSCs, making them unsuitable for elucidating the underlying mechanisms...
May 25, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28522430/the-drosophila-lin54-homolog-mip120-controls-two-aspects-of-oogenesis
#11
Mei-Hsin Cheng, Laura Andrejka, Paul J Vorster, Albert Hinman, Joseph S Lipsick
The conserved multi-protein MuvB core associates with the Myb oncoproteins and with the RB-E2F-DP tumor suppressor proteins in complexes that regulate cell proliferation, differentiation, and apoptosis. Drosophila Mip120, a homolog of LIN54, is a sequence-specific DNA-binding protein within the MuvB core. A mutant of Drosophila mip120 was previously shown to cause female and male sterility. We now show that Mip120 regulates two different aspects of oogenesis. First, in the absence of the Mip120 protein, egg chambers arrest during the transition from stage 7 to 8 with a failure of the normal program of chromosomal dynamics in the ovarian nurse cells...
May 18, 2017: Biology Open
https://www.readbyqxmd.com/read/28520736/the-bantam-microrna-acts-through-numb-to-exert-cell-growth-control-and-feedback-regulation-of-notch-in-tumor-forming-stem-cells-in-the-drosophila-brain
#12
Yen-Chi Wu, Kyu-Sun Lee, Yan Song, Stephan Gehrke, Bingwei Lu
Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28512144/tog-tubulin-binding-specificity-promotes-microtubule-dynamics-and-mitotic-spindle-formation
#13
Amy E Byrnes, Kevin C Slep
XMAP215, CLASP, and Crescerin use arrayed tubulin-binding tumor overexpressed gene (TOG) domains to modulate microtubule dynamics. We hypothesized that TOGs have distinct architectures and tubulin-binding properties that underlie each family's ability to promote microtubule polymerization or pause. As a model, we investigated the pentameric TOG array of a Drosophila melanogaster XMAP215 member, Msps. We found that Msps TOGs have distinct architectures that bind either free or polymerized tubulin, and that a polarized array drives microtubule polymerization...
June 5, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28508063/the-long-noncoding-rna-sprightly-acts-as-an-intranuclear-organizing-hub-for-pre-mrna-molecules
#14
Bongyong Lee, Anupama Sahoo, John Marchica, Erwin Holzhauser, Xiaoli Chen, Jian-Liang Li, Tatsuya Seki, Subramaniam Shyamala Govindarajan, Fatu Badiane Markey, Mona Batish, Sonali J Lokhande, Shaojie Zhang, Animesh Ray, Ranjan J Perera
Molecular mechanisms by which long noncoding RNA (lncRNA) molecules may influence cancerous condition are poorly understood. The aberrant expression of SPRIGHTLY lncRNA, encoded within the drosophila gene homolog Sprouty-4 intron, is correlated with a variety of cancers, including human melanomas. We demonstrate by SHAPE-seq and dChIRP that SPRIGHTLY RNA secondary structure has a core pseudoknotted domain. This lncRNA interacts with the intronic regions of six pre-mRNAs: SOX5, SMYD3, SND1, MEOX2, DCTN6, and RASAL2, all of which have cancer-related functions...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28505193/the-drosophila-orthologue-of-the-int6-onco-protein-regulates-mitotic-microtubule-growth-and-kinetochore-structure
#15
Fioranna Renda, Claudia Pellacani, Anton Strunov, Elisabetta Bucciarelli, Valeria Naim, Giuseppe Bosso, Elena Kiseleva, Silvia Bonaccorsi, David J Sharp, Alexey Khodjakov, Maurizio Gatti, Maria Patrizia Somma
INT6/eIF3e is a highly conserved component of the translation initiation complex that interacts with both the 26S proteasome and the COP9 signalosome, two complexes implicated in ubiquitin-mediated protein degradation. The INT6 gene was originally identified as the insertion site of the mouse mammary tumor virus (MMTV), and later shown to be involved in human tumorigenesis. Here we show that depletion of the Drosophila orthologue of INT6 (Int6) results in short mitotic spindles and deformed centromeres and kinetochores with low intra-kinetochore distance...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28492538/drosophila-caspase-activity-is-required-independently-of-apoptosis-to-produce-active-tnf-eiger-during-nociceptive-sensitization
#16
Juyeon Jo, Seol Hee Im, Daniel T Babcock, Srividya C Iyer, Felona Gunawan, Daniel N Cox, Michael J Galko
Tumor necrosis factor (TNF) signaling is required for inflammatory nociceptive (pain) sensitization in Drosophila and vertebrates. Nociceptive sensitization in Drosophila larvae following UV-induced tissue damage is accompanied by epidermal apoptosis and requires epidermal-derived TNF/Eiger and the initiator caspase, Dronc. Major gaps remain regarding TNF function in sensitization, including the relationship between apoptosis/tissue damage and TNF production, the downstream signaling in this context, and the target genes that modulate nociceptive behaviors...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28488382/neuron-specific-knockdown-of-the-drosophila-fat-induces-reduction-of-life-span-deficient-locomotive-ability-shortening-of-motoneuron-terminal-branches-and-defects-in-axonal-targeting
#17
Aya Nakamura, Ryo Tanaka, Kazushige Morishita, Hideki Yoshida, Yujiro Higuchi, Hiroshi Takashima, Masamitsu Yamaguchi
Mutations in FAT4 gene, one of the human FAT family genes, have been identified in Van Maldergem syndrome (VMS) and Hennekam lymphangiectasia-lymphedema syndrome (HS). The FAT4 gene encodes a large protein with extracellular cadherin repeats, EGF-like domains and Laminin G-like domains. FAT4 plays a role in tumor suppression and planar cell polarity. Drosophila contains a human FAT4 homologue, fat. Drosophila fat has been mainly studied with Drosophila eye and wing systems. Here, we specially knocked down Drosophila fat in nerve system...
May 9, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28480589/quantification-and-tracking-of-genetically-engineered-dendritic-cells-for-studying-immunotherapy
#18
Amnon Bar-Shir, Lina Alon, Michael J Korrer, Hong Seo Lim, Nirbhay N Yadav, Yoshinori Kato, Arvind P Pathak, Jeff W M Bulte, Assaf A Gilad
PURPOSE: Genetically encoded reporters can assist in visualizing biological processes in live organisms and have been proposed for longitudinal and noninvasive tracking of therapeutic cells in deep tissue. Cells can be labeled in situ or ex vivo and followed in live subjects over time. Nevertheless, a major challenge for reporter systems is to identify the cell population that actually expresses an active reporter. METHODS: We have used a nucleoside analog, pyrrolo-2'-deoxycytidine, as an imaging probe for the putative reporter gene, Drosophila melanogaster 2'-deoxynucleoside kinase...
May 7, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28476910/the-immune-phenotype-of-three-drosophila-leukemia-models
#19
Badrul Arefin, Martin Kunc, Robert Krautz, Ulrich Theopold
Many leukemia patients suffer from dysregulation of their immune system, making them more susceptible to infections and leading to general weakening (cachexia). Both adaptive and innate immunity are affected. The fruitfly Drosophila melanogaster has an innate immune system including cells of the myeloid lineage (hemocytes). To study Drosophila immunity and physiology during leukemia we established three models by driving expression of a dominant-active version of the Ras oncogene (Ras(V12) ) alone or combined with knockdowns of tumor suppressors in Drosophila hemocytes...
May 5, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28476861/the-centrioles-centrosomes-basal-bodies-and-cilia-of-drosophila-melanogaster
#20
Ramona Lattao, Levente Kovács, David M Glover
Centrioles play a key role in the development of the fly. They are needed for the correct formation of centrosomes, the organelles at the poles of the spindle that can persist as microtubule organizing centers (MTOCs) into interphase. The ability to nucleate cytoplasmic microtubules (MTs) is a property of the surrounding pericentriolar material (PCM). The centriole has a dual life, existing not only as the core of the centrosome but also as the basal body, the structure that templates the formation of cilia and flagellae...
May 2017: Genetics
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