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https://www.readbyqxmd.com/read/28719866/cell-competition-in-mammals-novel-homeostatic-machinery-for-embryonic-development-and-cancer-prevention
#1
REVIEW
Takeshi Maruyama, Yasuyuki Fujita
In the multi-cellular community, cells with different properties often compete with each other for survival and space. This process is named cell competition and was originally discovered in Drosophila. Recent studies have revealed that comparable phenomena also occur in mammals under various physiological and pathological conditions. Within the epithelium, normal cells often recognize the presence of the neighboring transformed cells and actively eliminate them from the epithelium; a process termed EDAC (Epithelial Defense Against Cancer)...
July 15, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#2
Rocío Simón, Carolina J Simoes da Silva, Sol Fereres, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
July 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28708826/intestinal-stem-cell-overproliferation-resulting-from-inactivation-of-the-apc-tumor-suppressor-requires-the-transcription-cofactors-earthbound-and-erect-wing
#3
Ai Tian, Hassina Benchabane, Zhenghan Wang, Chloe Zimmerman, Nan Xin, Jessica Perochon, Gabriela Kalna, Owen J Sansom, Chao Cheng, Julia B Cordero, Yashi Ahmed
Wnt/β-catenin signal transduction directs intestinal stem cell (ISC) proliferation during homeostasis. Hyperactivation of Wnt signaling initiates colorectal cancer, which most frequently results from truncation of the tumor suppressor Adenomatous polyposis coli (APC). The β-catenin-TCF transcription complex activates both the physiological expression of Wnt target genes in the normal intestinal epithelium and their aberrantly increased expression in colorectal tumors. Whether mechanistic differences in the Wnt transcription machinery drive these distinct levels of target gene activation in physiological versus pathological states remains uncertain, but is relevant for the design of new therapeutic strategies...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28701960/role-of-mitochondrial-reverse-electron-transport-in-ros-signaling-potential-roles-in-health-and-disease
#4
REVIEW
Filippo Scialò, Daniel J Fernández-Ayala, Alberto Sanz
Reactive Oxygen Species (ROS) can cause oxidative damage and have been proposed to be the main cause of aging and age-related diseases including cancer, diabetes and Parkinson's disease. Accordingly, mitochondria from old individuals have higher levels of ROS. However, ROS also participate in cellular signaling, are instrumental for several physiological processes and boosting ROS levels in model organisms extends lifespan. The current consensus is that low levels of ROS are beneficial, facilitating adaptation to stress via signaling, whereas high levels of ROS are deleterious because they trigger oxidative stress...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28701701/systematic-discovery-of-genetic-modulation-by-jumonji-histone-demethylases-in-drosophila
#5
Nevine A Shalaby, Raheel Sayed, Qiao Zhang, Shane Scoggin, Susan Eliazer, Adrian Rothenfluh, Michael Buszczak
Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, developmental and neurological disorders, however, the shared biology and possible common contribution to organismal development and tissue homeostasis of all JmjC proteins remains unclear. Here, we systematically tested the function of all 13 Drosophila JmjC genes...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28688927/an-unexpected-friend-ros-in-apoptosis-induced-compensatory-proliferation-implications-for-regeneration-and-cancer
#6
REVIEW
Neha Diwanji, Andreas Bergmann
Apoptosis-induced compensatory proliferation (AiP) is a form of compensatory proliferation that is triggered by apoptotic cell death to maintain tissue homeostasis. As such, AiP is essential for many tissue repair processes including regeneration. The apoptotic effectors, termed caspases, not only execute apoptosis, but are also directly involved in the generation of the signals required for AiP. Reactive oxygen species (ROS) play an important role for regenerative processes. Recently, it was shown in Drosophila that apoptotic caspases can mediate the generation of ROS for promoting AiP...
July 5, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28687780/nuclear-receptors-connect-progenitor-transcription-factors-to-cell-cycle-control
#7
Marta Neto, Marina Naval-Sánchez, Delphine Potier, Paulo S Pereira, Dirk Geerts, Stein Aerts, Fernando Casares
The specification and growth of organs is controlled simultaneously by networks of transcription factors. While the connection between these transcription factors with fate determinants is increasingly clear, how they establish the link with the cell cycle is far less understood. Here we investigate this link in the developing Drosophila eye, where two transcription factors, the MEIS1 homologue hth and the Zn-finger tsh, synergize to stimulate the proliferation of naïve eye progenitors. Experiments combining transcriptomics, open-chromatin profiling, motif analysis and functional assays indicate that these progenitor transcription factors exert a global regulation of the proliferation program...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678789/egfr-controls-drosophila-tracheal-tube-elongation-by-intracellular-trafficking-regulation
#8
Ivette Olivares-Castiñeira, Marta Llimargas
Development is governed by a few conserved signalling pathways. Amongst them, the EGFR pathway is used reiteratively for organ and tissue formation, and when dysregulated can lead to cancer and metastasis. Given its relevance, identifying its downstream molecular machinery and understanding how it instructs cellular changes is crucial. Here we approach this issue in the respiratory system of Drosophila. We identify a new role for EGFR restricting the elongation of the tracheal Dorsal Trunk. We find that EGFR regulates the apical determinant Crb and the extracellular matrix regulator Serp, two factors previously known to control tube length...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28673935/functions-of-long-non-coding-rnas-in-human-disease-and-their-conservation-in-drosophila-development
#9
REVIEW
Oliver M Rogoyski, Jose Ignacio Pueyo, Juan Pablo Couso, Sarah F Newbury
Genomic analysis has found that the transcriptome in both humans and Drosophila melanogaster features large numbers of long non-coding RNA transcripts (lncRNAs). This recently discovered class of RNAs regulates gene expression in diverse ways and has been involved in a large variety of important biological functions. Importantly, an increasing number of lncRNAs have also been associated with a range of human diseases, including cancer. Comparative analyses of their functions among these organisms suggest that some of their modes of action appear to be conserved...
July 3, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28669782/the-drosophila-melanogaster-tribbles-pseudokinase-is-necessary-for-proper-memory-formation
#10
Holly LaFerriere, Troy Zars
The tribbles (trbl) pseudokinases play important roles in signaling and physiology in multiple contexts, ranging from innate immunity to cancer, suggesting fundamental cellular functions for the trbls' gene products. Despite expression of the trbl pseudokinases in the nervous systems of invertebrate and vertebrate animals, and evidence that they have a function within mouse and human dopamine neurons, there is no clear case for a function of a Trbl protein that influences behavior. Indeed, the first and only evidence for this type of function comes from Drosophila melanogaster, where a mutation of the single trbl gene was identified in a genetic screen for short-term memory mutant flies...
June 29, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28665982/the-sertad-protein-taranis-plays-a-role-in-polycomb-mediated-gene-repression
#11
Pranabananda Dutta, Willis X Li
The Polycomb group (PcG) proteins have been implicated in epigenetic transcriptional repression in development, stem cell maintenance and in cancer. The chromodomain protein Polycomb (Pc) is a key member of the PcG. Pc binds to the histone mark, trimethylated histone 3 lysine 27 (H3K27me3), to initiate transcriptional repression. How PcG proteins are recruited to target loci is not fully understood. Here we show that the Drosophila SERTA domain protein Taranis (Tara) is involved in transcriptional regulation of Pc target genes...
2017: PloS One
https://www.readbyqxmd.com/read/28665616/quantitative-proteomics-reveals-extensive-changes-in-the-ubiquitinome-after-perturbation-of-the-proteasome-by-targeted-dsrna-mediated-subunit-knockdown-in-drosophila
#12
Karen A Sap, Karel Bezstarosti, Dick H W Dekkers, Olaf Voets, Jeroen A A Demmers
The ubiquitin-proteasome system (UPS), a highly regulated mechanism including the active marking of proteins by ubiquitin to be degraded, is critical in regulating proteostasis. Dysfunctioning of the UPS has been implicated in diseases such as cancer and neurodegenerative disorders. Here we investigate the effects of proteasome malfunctioning on global proteome and ubiquitinome dynamics using SILAC proteomics in Drosophila S2 cells. dsRNA-mediated knockdown of specific proteasome target subunits is used to inactivate the proteasome...
July 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28660757/pulsed-epr-insights-into-the-ligand-environment-of-copper-in-drosophila-lysyl-oxidase
#13
Guodong Rao, Sandhya Bansal, Wen Xuan Law, Bing O'Dowd, Sergei A Dikanov, Eric Oldfield
Lysyl oxidase is a copper amine oxidase that crosslinks collagens and elastin in connective tissue and plays an important role in fibrosis, cancer development and formation of the "metastatic niche". Despite its important biological functions, the structure of human LOX remains unknown (unlike that of an unrelated LOX, from Pichia pastoris). Here, we expressed active LOX from Drosophila melanogaster, DmLOXL1, a close homologue of human LOX, and characterized it by MS, UV-Vis, activity and inhibition assays...
June 29, 2017: Biochemistry
https://www.readbyqxmd.com/read/28658615/pp6-disruption-synergizes-with-oncogenic-ras-to-promote-jnk-dependent-tumor-growth-and-invasion
#14
Xianjue Ma, Jin-Yu Lu, Yongli Dong, Daming Li, Juan N Malagon, Tian Xu
RAS genes are frequently mutated in cancers, yet an effective treatment has not been developed, partly because of an incomplete understanding of signaling within Ras-related tumors. To address this, we performed a genetic screen in Drosophila, aiming to find mutations that cooperate with oncogenic Ras (Ras(V12)) to induce tumor overgrowth and invasion. We identified fiery mountain (fmt), a regulatory subunit of the protein phosphatase 6 (PP6) complex, as a tumor suppressor that synergizes with Ras(V12) to drive c-Jun N-terminal kinase (JNK)-dependent tumor growth and invasiveness...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28644726/cytotoxic-and-genotoxic-actions-of-casiopeina-iii-ea-cas-iii-ea-in-somatic-and-germ-cells-of-drosophila-melanogaster
#15
L M Vidal, E Pimentel, M P Cruces, S Hernández, L Ruiz-Azuara
Casiopeinas® are a group of newly synthesized drugs designed to treat cancer. These copper (Cu) complexes exhibit cytostatic, cytotoxic, genotoxic, and antineoplastic activities through different mechanisms of action. To evaluate the influence of these compounds, some in vivo studies were performed using predominantly somatic cells. The aim of the present study was to examine the cytotoxic and genotoxic actions of Casiopeina III-Ea (Cas III-Ea) in somatic as well as germ cells of Drosophila melanogaster. For cytotoxicity, the productivity and some morphometric parameters were measured and genotoxicity was assessed by means of the somatic mutation and recombination test assay in the wing...
2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28640815/an-autonomous-metabolic-role-for-spen
#16
Kelsey E Hazegh, Travis Nemkov, Angelo D'Alessandro, John D Diller, Jenifer Monks, James L McManaman, Kenneth L Jones, Kirk C Hansen, Tânia Reis
Preventing obesity requires a precise balance between deposition into and mobilization from fat stores, but regulatory mechanisms are incompletely understood. Drosophila Split ends (Spen) is the founding member of a conserved family of RNA-binding proteins involved in transcriptional regulation and frequently mutated in human cancers. We find that manipulating Spen expression alters larval fat levels in a cell-autonomous manner. Spen-depleted larvae had defects in energy liberation from stores, including starvation sensitivity and major changes in the levels of metabolic enzymes and metabolites, particularly those involved in β-oxidation...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28623304/identification-of-transcripts-with-short-stuorfs-as-targets-for-denr%C3%A2-mcts1-dependent-translation-in-human-cells
#17
Sibylle Schleich, Julieta M Acevedo, Katharina Clemm von Hohenberg, Aurelio A Teleman
The non-canonical initiation factors DENR and MCTS1 have been linked to cancer and autism. We recently showed in Drosophila that DENR and MCTS1 regulate translation re-initiation on transcripts containing upstream Open Reading Frames (uORFs) with strong Kozak sequences (stuORFs). Due to the medical relevance of DENR and MCTS1, it is worthwhile identifying the transcripts in human cells that depend on DENR and MCTS1 for their translation. We show here that in humans, as in Drosophila, transcripts with short stuORFs require DENR and MCTS1 for their optimal expression...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619822/cop9-signalosome-subunits-protect-capicua-from-map-kinase-dependent-and-independent-mechanisms-of-degradation
#18
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/28612512/the-germline-factor-ddx4-functions-in-blood-derived-cancer-cell-phenotypes
#19
Natalie Schudrowitz, Satoshi Takagi, Gary M Wessel, Mamiko Yajima
DDX4 (the human ortholog of Drosophila Vasa) is an RNA helicase and is present in the germ lines of all metazoans tested. It was historically thought to be expressed specifically in germline cells, but with additional organisms studied, it is now clear that in some animals DDX4/Vasa functions outside of the germline, in a variety of somatic cells in the embryo and adult. In this report, we document that DDX4 is widely expressed in soma-derived cancer cell lines, including myeloma (IM-9) and leukemia (THP-1) cells...
June 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28588207/capping-enzyme-mrna-cap-rngtt-regulates-hedgehog-pathway-activity-by-antagonizing-protein-kinase-a
#20
Ping Chen, Zizhang Zhou, Xia Yao, Shu Pang, Meijing Liu, Weirong Jiang, Jin Jiang, Qing Zhang
Hedgehog (Hh) signaling plays a pivotal role in animal development and its deregulation in humans causes birth defects and several types of cancer. Protein Kinase A (PKA) modulates Hh signaling activity through phosphorylating the transcription factor Cubitus interruptus (Ci) and G protein coupled receptor (GPCR) family protein Smoothened (Smo) in Drosophila, but how PKA activity is regulated remains elusive. Here, we identify a novel regulator of the Hh pathway, the capping-enzyme mRNA-cap, which positively regulates Hh signaling activity through modulating PKA activity...
June 6, 2017: Scientific Reports
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