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https://www.readbyqxmd.com/read/27916526/the-mitochondrial-lon-protease-is-required-for-age-specific-and-sex-specific-adaptation-to-oxidative-stress
#1
Laura C D Pomatto, Caroline Carney, Brenda Shen, Sarah Wong, Kelly Halaszynski, Matthew P Salomon, Kelvin J A Davies, John Tower
Multiple human diseases involving chronic oxidative stress show a significant sex bias, including neurodegenerative diseases, cancer, immune dysfunction, diabetes, and cardiovascular disease. However, a possible molecular mechanism for the sex bias in physiological adaptation to oxidative stress remains unclear. Here, we report that Drosophila melanogaster females but not males adapt to hydrogen peroxide stress, whereas males but not females adapt to paraquat (superoxide) stress. Stress adaptation in each sex requires the conserved mitochondrial Lon protease and is associated with sex-specific expression of Lon protein isoforms and proteolytic activity...
November 23, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27916025/the-role-of-the-extracellular-biophysical-cues-in-modulating-hippo-yap-pathway
#2
Jung-Soon Mo
The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. In Drosophila and vertebrates, it consists of a highly conserved kinase cascade, which involve MST and Lats that negatively regulate the activity of downstream transcription coactivators, YAP and TAZ. Through its interaction with TEADs and other transcription factors, they mediate both proliferative and antiapoptotic gene expression and thus regulate tissue repair and regeneration. Dysregulation or mutation of the Hippo pathway is linked to tumorigenesis and cancer development...
December 5, 2016: BMB Reports
https://www.readbyqxmd.com/read/27898892/transcriptome-analyses-identify-five-transcription-factors-differentially-expressed-in-the-hypothalamus-of-post-versus-prepubertal-brahman-heifers
#3
M R S Fortes, L T Nguyen, M M D C A Weller, A Cánovas, A Islas-Trejo, L R Porto-Neto, A Reverter, S A Lehnert, G B Boe-Hansen, M G Thomas, J F Medrano, S S Moore
Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus...
September 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27897178/functional-exploration-of-colorectal-cancer-genomes-using-drosophila
#4
Erdem Bangi, Claudio Murgia, Alexander G S Teague, Owen J Sansom, Ross L Cagan
The multigenic nature of human tumours presents a fundamental challenge for cancer drug discovery. Here we use Drosophila to generate 32 multigenic models of colon cancer using patient data from The Cancer Genome Atlas. These models recapitulate key features of human cancer, often as emergent properties of multigenic combinations. Multigenic models such as ras p53 pten apc exhibit emergent resistance to a panel of cancer-relevant drugs. Exploring one drug in detail, we identify a mechanism of resistance for the PI3K pathway inhibitor BEZ235...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27891621/animal-cryptochromes-divergent-roles-in-light-perception-circadian-timekeeping-and-beyond
#5
Alicia K Michael, Jennifer L Fribourgh, Russell N Van Gelder, Carrie L Partch
Cryptochromes are evolutionarily related to the light-dependent DNA repair enzyme photolyase, serving as major regulators of circadian rhythms in insects and vertebrate animals. There are two types of cryptochromes in the animal kingdom: Drosophila-like CRYs that act as non-visual photopigments linking circadian rhythms to the environmental light/dark cycle, and vertebrate-like CRYs that do not appear to sense light directly, but control the generation of circadian rhythms by acting as transcriptional repressors...
November 28, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27872203/molecular-mechanisms-of-asymmetric-divisions-in-mammary-stem-cells
#6
REVIEW
Angela Santoro, Thalia Vlachou, Manuel Carminati, Pier Giuseppe Pelicci, Marina Mapelli
Stem cells have the remarkable ability to undergo proliferative symmetric divisions and self-renewing asymmetric divisions. Balancing of the two modes of division sustains tissue morphogenesis and homeostasis. Asymmetric divisions of Drosophila neuroblasts (NBs) and sensory organ precursor (SOP) cells served as prototypes to learn what we consider now principles of asymmetric mitoses. They also provide initial evidence supporting the notion that aberrant symmetric divisions of stem cells could correlate with malignancy...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27872148/proteomics-screen-identifies-class-i-rab11-fips-as-key-regulators-of-cytokinesis
#7
Carl Laflamme, Jacob A Galan, Khaled Ben El Kadhi, Antoine Méant, Carlos Zeledon, Sébastien Carréno, Philippe P Roux, Gregory Emery
The 14-3-3 protein family orchestrates a complex network of molecular interactions that regulates various biological processes. Owing to their role in regulating the cell cycle and protein trafficking, 14-3-3 proteins are prevalent in human diseases, such as cancer, diabetes and neurodegeneration. 14-3-3 proteins are expressed in all eukaryotic cells, suggesting that they mediate their biological functions through evolutionarily conserved protein interactions. To identify these core 14-3-3 client proteins, we used an affinity-based proteomics approach to characterize and compare the human and Drosophila 14-3-3 interactome...
November 21, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27856247/the-drosophila-f-box-protein-slimb-controls-dsmurf-protein-turnover-to-regulate-the-hippo-pathway
#8
Liangchang Hu, Ping Wang, Runan Zhao, Shanshan Li, Feng Wang, Chaojie Li, Lei Cao, Shian Wu
SMAD ubiquitination regulatory factors 1 and 2 (Smurf1/2) are members of the HECT domain E3 ligase family which play crucial roles in the regulation of cell cycle progression, planar cell polarity, cancer metastasis and cell apoptosis. We recently showed that the Drosophila homolog dSmurf controls the stability of Warts kinase to regulate the Hippo pathway. In the current study, we found that the F-box protein Slimb controls dSmurf protein level to regulate the Hippo pathway. Slimb physically associates with dSmurf as revealed by co-immunoprecipitation assay in S2 cells...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27852975/rpd3-interacts-with-insulin-signaling-in-drosophila-longevity-extension
#9
Jared K Woods, Tahereh Ziafazeli, Blanka Rogina
Histone deacetylase (HDAC) 1 regulates chromatin compaction and gene expression by removing acetyl groups from lysine residues within histones. HDAC1 affects a variety of processes including proliferation, development, metabolism, and cancer. Reduction or inhibition of Rpd3, yeast and fly HDAC1 orthologue, extends longevity. However, the mechanism of rpd3's effects on longevity remains unclear. Here we report an overlap between rpd3 and the Insulin/Insulin-like growth factor signaling (IIS) longevity pathways...
November 14, 2016: Aging
https://www.readbyqxmd.com/read/27835572/sprouty2-inhibits-amphiregulin-induced-down-regulation-of-e-cadherin-and-cell-invasion-in-human-ovarian-cancer-cells
#10
Jung-Chien Cheng, Hsun-Ming Chang, Siyuan Xiong, Wai-Kin So, Peter C K Leung
Similar to Drosophila Sprouty (SPRY), mammalian SPRY proteins inhibit the receptor tyrosine kinase-mediated activation of cellular signaling pathways. SPRY2 expression levels have been shown to be down-regulated in human ovarian cancer, and patients with low SPRY2 expression have significantly poorer survival than those with high SPRY2 expression. In addition, epidermal growth factor receptor (EGFR) is overexpressed in human ovarian cancer and is associated with more aggressive clinical behavior and a poor prognosis...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27830090/drosophila-enhancer-of-rudimentary-homolog-erh-is-a-binding-partner-of-rps3-rpl19-and-ddit4-suggesting-a-mechanism-for-the-nuclear-localization-of-erh
#11
Stuart I Tsubota, Anthony C Phillips
The protein enhancer of rudimentary homolog, ERH, is a small, highly conserved protein that has been found in animals, plants, and protists. Genetic and biochemical interactions have implicated ERH in the regulation of pyrimidine biosynthesis, DNA replication, transcription, mRNA splicing, cellular proliferation, tumorigenesis, and the Notch signaling pathway. In vertebrates and insects, ERH is nuclearly localized; however, an examination of the ERH amino-acid sequence does not reveal any nuclear localization signals...
2016: Molecular Biology International
https://www.readbyqxmd.com/read/27812882/induction-and-detection-of-oncogene-induced-cellular-senescence-in-drosophila
#12
Mai Nakamura, Tatsushi Igaki
Cellular senescence is induced by various cellular stresses, including activation of the Ras oncogene. In Drosophila imaginal epithelia, clones of cells expressing oncogenic Ras (Ras(V12)) show several markers of cellular senescence, such as elevation of SA-β-gal activity, upregulation of the Cdk inhibitor Dacapo (Dap), and heterochromatinization. However, these cells do not undergo cell cycle arrest or exhibit a DNA damage response (DDR), cellular hypertrophy, or a senescence-associated secretory phenotype (SASP), other essential markers of cellular senescence...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27765583/cisplatin-induces-mitochondrial-deficits-in-drosophila-larval-segmental-nerve
#13
Jewel L Podratz, Han Lee, Patrizia Knorr, Stephanie Koehler, Steven Forsythe, Kelsey Lambrecht, Suzette Arias, Kiley Schmidt, Gabrielle Steinhoff, Georgiy Yudintsev, Amy Yang, Eugenia Trushina, Anthony Windebank
Cisplatin is an effective chemotherapy drug that induces peripheral neuropathy in cancer patients. In rodent dorsal root ganglion neurons, cisplatin binds nuclear and mitochondrial DNA (mtDNA) inducing DNA damage and apoptosis. Platinum-mtDNA adducts inhibit mtDNA replication and transcription leading to mitochondrial degradation. Cisplatin also induces climbing deficiencies associated with neuronal apoptosis in adult Drosophila melanogaster. Here we used Drosophila larvae that express green fluorescent protein in the mitochondria of motor neurons to observe the effects of cisplatin on mitochondrial dynamics and function...
January 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27743477/frazzled-promotes-growth-cone-attachment-at-the-source-of-a-netrin-gradient-in-the-drosophila-visual-system
#14
Orkun Akin, S Lawrence Zipursky
Axon guidance is proposed to act through a combination of long- and short-range attractive and repulsive cues. The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both long- and short-range guidance. In the Drosophila visual system, R8 photoreceptor growth cones were shown to require Net-Fra to reach their target, the peak of a Net gradient. Using live imaging, we show, however, that R8 growth cones reach and recognize their target without Net, Fra, or Trim9, a conserved binding partner of Fra, but do not remain attached to it...
October 15, 2016: ELife
https://www.readbyqxmd.com/read/27729408/dna-damage-induced-lok-chk2-activation-compromises-germline-stem-cell-self-renewal-and-lineage-differentiation
#15
Xing Ma, Yingying Han, Xiaoqing Song, Trieu Do, Zhihao Yang, Jianquan Ni, Ting Xie
Stem cells in adult tissues are constantly exposed to genotoxic stress and also accumulate DNA damage with age. However, it remains largely unknown how DNA damage affects both stem cell self-renewal and differentiation. In this study, we show that DNA damage retards germline stem cell (GSC) self-renewal and progeny differentiation in a Lok kinase-dependent manner in the Drosophila ovary. Both heatshock-inducible endonuclease I-CreI expression and X-ray irradiation can efficiently introduce double-strand breaks in GSCs and their progeny, resulting in a rapid GSC loss and a GSC progeny differentiation defect...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27702999/ohgata-the-single-drosophila-ortholog-of-human-cereblon-regulates-insulin-signaling-dependent-organismic-growth
#16
Satoru Wakabayashi, Naoya Sawamura, André Voelzmann, Meike Broemer, Toru Asahi, Michael Hoch
Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that is highly conserved in animals and plants. CRBN proteins have been implicated in various biological processes such as development, metabolism, learning, and memory formation, and their impairment has been linked to autosomal recessive non-syndromic intellectual disability and cancer. Furthermore, human CRBN was identified as the primary target of thalidomide teratogenicity. Data on functional analysis of CRBN family members in vivo, however, are still scarce...
November 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27694890/an-interaction-between-scribble-and-the-nadph-oxidase-complex-controls-m1-macrophage-polarization-and-function
#17
Weiyue Zheng, Masataka Umitsu, Ishaan Jagan, Charles W Tran, Noboru Ishiyama, Michael BeGora, Kiyomi Araki, Pamela S Ohashi, Mitsuhiko Ikura, Senthil K Muthuswamy
The polarity protein Scribble (SCRIB) regulates apical-basal polarity, directional migration and tumour suppression in Drosophila and mammals. Here we report that SCRIB is an important regulator of myeloid cell functions including bacterial infection and inflammation. SCRIB interacts directly with the NADPH oxidase (NOX) complex in a PSD95/Dlg/ZO-1 (PDZ)-domain-dependent manner and is required for NOX-induced reactive oxygen species (ROS) generation in culture and in vivo. On bacterial infection, SCRIB localized to phagosomes in a leucine-rich repeat-dependent manner and promoted ROS production within phagosomes to kill bacteria...
October 3, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27693136/centrosome-amplification-increases-single-cell-branching-in-post-mitotic-cells
#18
Delia Ricolo, Myrto Deligiannaki, Jordi Casanova, Sofia J Araújo
Centrosome amplification is a hallmark of cancer, although we are still far from understanding how this process affects tumorigenesis [1, 2]. Besides the contribution of supernumerary centrosomes to mitotic defects, their biological effects in the post-mitotic cell are not well known. Here, we exploit the effects of centrosome amplification in post-mitotic cells during single-cell branching. We show that Drosophila tracheal cells with extra centrosomes branch more than wild-type cells. We found that mutations in Rca1 and CycA affect subcellular branching, causing tracheal tip cells to form more than one subcellular lumen...
September 17, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27687497/antagonistic-roles-of-drosophila-tctp-and-brahma-in-chromatin-remodelling-and-stabilizing-repeated-sequences
#19
Sung-Tae Hong, Kwang-Wook Choi
Genome stability is essential for all organisms. Translationally controlled tumour protein (TCTP) is a conserved protein associated with cancers. TCTP is involved in multiple intracellular functions, but its role in transcription and genome stability is poorly understood. Here, we demonstrate new functions of Drosophila TCTP (Tctp) in transcription and the stability of repeated sequences (rDNA and pericentromeric heterochromatin). Tctp binds Brahma (Brm) chromatin remodeler to negatively modulate its activity...
2016: Nature Communications
https://www.readbyqxmd.com/read/27680705/the-lipolysis-pathway-sustains-normal-and-transformed-stem-cells-in-adult-drosophila
#20
Shree Ram Singh, Xiankun Zeng, Jiangsha Zhao, Ying Liu, Gerald Hou, Hanhan Liu, Steven X Hou
Cancer stem cells (CSCs) may be responsible for tumour dormancy, relapse and the eventual death of most cancer patients. In addition, these cells are usually resistant to cytotoxic conditions. However, very little is known about the biology behind this resistance to therapeutics. Here we investigated stem-cell death in the digestive system of adult Drosophila melanogaster. We found that knockdown of the coat protein complex I (COPI)-Arf79F (also known as Arf1) complex selectively killed normal and transformed stem cells through necrosis, by attenuating the lipolysis pathway, but spared differentiated cells...
September 28, 2016: Nature
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