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https://www.readbyqxmd.com/read/28215940/elf5-is-a-principal-cell-lineage-specific-transcription-factor-in-the-kidney-that-contributes-to-aqp2-and-avpr2-gene-expression
#1
Justin Grassmeyer, Malini Mukherjee, Jennifer deRiso, Casey Hettinger, Monica Bailey, Satrajit Sinha, Jane E Visvader, Haotian Zhao, Eric Fogarty, Kameswaran Surendran
The mammalian kidney collecting ducts are critical for water, electrolyte and acid-base homeostasis and develop as a branched network of tubular structures composed of principal cells intermingled with intercalated cells. The intermingled nature of the different collecting duct cell types has made it challenging to identify unique and critical factors that mark and/or regulate the development of the different collecting duct cell lineages. Here we report that the canonical Notch signaling pathway components, RBPJ and Presinilin1 and 2, are involved in patterning the mouse collecting duct cell fates by maintaining a balance between principal cell and intercalated cell fates...
February 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28163017/small-molecule-inhibitors-of-the-sox18-transcription-factor
#2
Frank Fontaine, Jeroen Overman, Mehdi Moustaqil, Sreeman Mamidyala, Angela Salim, Kamesh Narasimhan, Nina Prokoph, Avril A B Robertson, Linda Lua, Kirill Alexandrov, Peter Koopman, Robert J Capon, Emma Sierecki, Yann Gambin, Ralf Jauch, Matthew A Cooper, Johannes Zuegg, Mathias Francois
Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In an attempt to modulate the activity of SOX18 TF, a known regulator of vascular growth in development and disease, we screened a marine extract library for potential small-molecule inhibitors...
January 27, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28160419/adams-oliver-syndrome-review-of-the-literature-refining-the-diagnostic-phenotype
#3
Susan Hassed, Shibo Li, John Mulvihill, Christopher Aston, Susan Palmer
The Adams-Oliver syndrome (AOS) is defined as aplasia cutis congenita (ACC) with transverse terminal limb defects (TTLD). Frequencies of associated anomalies are not well characterized. Six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. We review 385 previously described individuals (139 non-familial and 246 familial probands and family members) and add clinical data on 13 previously unreported individuals with AOS. In addition to ACC and TTLD, the most commonly associated anomalies included a wide variety of central nervous system (CNS) anomalies and congenital heart defects each seen in 23%...
February 4, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28030855/a-rare-de-novo-interstitial-duplication-at-4p15-2-in-a-boy-with-severe-congenital-heart-defects-limb-anomalies-hypogonadism-and-global-developmental-delay
#4
Liyang Liang, Yingjun Xie, Yiping Shen, Qibin Yin, Haiming Yuan
Proximal 4p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafe-au-lait spots, developmental delay, tall and thin habitus, and intellectual disability. At present, over 20 cases of this syndrome have been published. However, duplication of the same region in proximal 4p has never been reported. Here, we describe a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre- and postnatal developmental delay, and mild cognitive impairments...
2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28027012/dynamic-chromatin-regulation-at-notch-target-genes
#5
Benedetto Daniele Giaimo, Franz Oswald, Tilman Borggrefe
RBPJ is the central transcription factor that controls the Notch-dependent transcriptional response by coordinating repressing histone H3K27 deacetylation and activating histone H3K4 methylation. Here, we discuss the molecular mechanisms how RBPJ interacts with opposing NCoR/HDAC-corepressing or KMT2D/UTX-coactivating complexes and how this is controlled by phosphorylation of chromatin modifiers.
January 2017: Transcription
https://www.readbyqxmd.com/read/28009085/protein-tyrosine-phosphatase-prl2-mediates-notch-and-kit-signals-in-early-t-cell-progenitors
#6
Michihiro Kobayashi, Sarah C Nabinger, Yunpeng Bai, Momoko Yoshimoto, Rui Gao, Sisi Chen, Chonghua Yao, Yuanshu Dong, Lujuan Zhang, Sonia Rodriguez, Yumi Yashiro-Ohtani, Warren S Pear, Nadia Carlesso, Mervin C Yoder, Reuben Kapur, Mark H Kaplan, Hugo Daniel Lacorazza, Zhong-Yin Zhang, Yan Liu
The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors...
December 23, 2016: Stem Cells
https://www.readbyqxmd.com/read/27939883/indispensable-role-of-notch-ligand-dependent-signaling-in-the-proliferation-and-stem-cell-niche-maintenance-of-apc-deficient-intestinal-tumors
#7
Toru Nakata, Hiromichi Shimizu, Sayaka Nagata, Go Ito, Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Fumiaki Ishibashi, Reiko Kuno, Sho Anzai, Tatsuro Murano, Tomohiro Mizutani, Shigeru Oshima, Kiichiro Tsuchiya, Tetsuya Nakamura, Katsuto Hozumi, Mamoru Watanabe, Ryuichi Okamoto
Ligand-dependent activation of Notch signaling is required to maintain the stem-cell niche of normal intestinal epithelium. However, the precise role of Notch signaling in the maintenance of the intestinal tumor stem cell niche and the importance of the RBPJ-independent non-canonical pathway in intestinal tumors remains unknown. Here we show that Notch signaling was activated in LGR5(+ve) cells of APC-deficient mice intestinal tumors. Accordingly, Notch ligands, including Jag1, Dll1, and Dll4, were expressed in these tumors...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27936142/gene-co-expression-network-analysis-unraveling-transcriptional-regulation-of-high-altitude-adaptation-of-tibetan-pig
#8
Cunling Jia, Xiaoyan Kong, James E Koltes, Xiao Gou, Shuli Yang, Dawei Yan, Shaoxiong Lu, Zehui Wei
Tibetan pigs have survived at high altitude for millennia and they have a suite of adaptive features to tolerate the hypoxic environment. However, the molecular mechanisms underlying the regulation of hypoxia-adaptive phenotypes have not been completely elucidated. In this study, we analyzed differentially expressed genes (DEGs), biological pathways and constructed co-expression regulation networks using whole-transcriptome microarrays from lung tissues of Tibetan and Duroc pigs both at high and low altitude...
2016: PloS One
https://www.readbyqxmd.com/read/27904763/microrna-133a-3p-exerts-inhibitory-effects-on-gallbladder-carcinoma-via-targeting-rbpj
#9
Yuan Huang, Yaoshi Wu, Jiahong Dong, Dongdong Han, Shiwei Yang, Lin Jiang
Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with high mortality. The median survival time is 6 months, and the 5-year survival rate less than 5% for GBC patients. Thus, it is imperative to investigate the molecular mechanisms underlying the pathogenesis of GBC. miR-133a may exert anti-tumor effects on a variety of cancers. However, the role of miR-133a in the pathogenesis of GBC remains unclear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) showed the miR-133a-3p expression markedly decreased in GBC as compared to adjacent normal tissues...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27791012/notch3-drives-development-and-progression-of-cholangiocarcinoma
#10
Rachel V Guest, Luke Boulter, Benjamin J Dwyer, Timothy J Kendall, Tak-Yung Man, Sarah E Minnis-Lyons, Wei-Yu Lu, Andrew J Robson, Sofia Ferreira Gonzalez, Alexander Raven, Davina Wojtacha, Jennifer P Morton, Mina Komuta, Tania Roskams, Stephen J Wigmore, Owen J Sansom, Stuart J Forbes
The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27708688/the-csl-proteins-versatile-transcription-factors-and-context-dependent-corepressors-of-the-notch-signaling-pathway
#11
REVIEW
Humberto Contreras-Cornejo, Germán Saucedo-Correa, Javier Oviedo-Boyso, Juan José Valdez-Alarcón, Víctor Manuel Baizabal-Aguirre, Marcos Cajero-Juárez, Alejandro Bravo-Patiño
The Notch signaling pathway is a reiteratively used cell to cell communication pathway that triggers pleiotropic effects. The correct regulation of the pathway permits the efficient regulation of genes involved in cell fate decision throughout development. This activity relies notably on the CSL proteins, (an acronym for CBF-1/RBPJ-κ in Homo sapiens/Mus musculus respectively, Suppressor of Hairless in Drosophila melanogaster, Lag-1 in Caenorhabditis elegans) which is the unique transcription factor and DNA binding protein involved in this pathway...
2016: Cell Division
https://www.readbyqxmd.com/read/27695000/initial-seeding-of-the-embryonic-thymus-by-immune-restricted-lympho-myeloid-progenitors
#12
Tiago C Luis, Sidinh Luc, Takuo Mizukami, Hanane Boukarabila, Supat Thongjuea, Petter S Woll, Emanuele Azzoni, Alice Giustacchini, Michael Lutteropp, Tiphaine Bouriez-Jones, Harsh Vaidya, Adam J Mead, Deborah Atkinson, Charlotta Böiers, Joana Carrelha, Iain C Macaulay, Roger Patient, Frederic Geissmann, Claus Nerlov, Rickard Sandberg, Marella F T R de Bruijn, C Clare Blackburn, Isabelle Godin, Sten Eirik W Jacobsen
The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-IPs) before their entry into the thymus and activation of Notch signaling. T-IPs did not include multipotent stem cells or molecular evidence of T cell-restricted progenitors...
December 2016: Nature Immunology
https://www.readbyqxmd.com/read/27587543/polymorphisms-in-cancer-related-pathway-genes-and-lung-cancer
#13
Shin Yup Lee, Hyo-Gyoung Kang, Jin Eun Choi, Deuk Kju Jung, Won Kee Lee, Hyun Chul Lee, So Yeon Lee, Seung Soo Yoo, Jaehee Lee, Yangki Seok, Eung Bae Lee, Seung Ick Cha, Sukki Cho, Chang Ho Kim, Myung Hoon Lee, Jae Yong Park
We evaluated the associations between potentially functional variants in a comprehensive list of cancer-related genes and lung cancer in a Korean population.A total of 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes involved in carcinogenesis were evaluated using an Affymetrix custom-made GeneChip in 610 nonsmall cell lung cancer patients and 610 healthy controls. A replication study was conducted in an independent set of 490 cases and 486 controls. 68 SNPs were significantly associated with lung cancer in the discovery set and tested for replication...
October 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27496872/endothelial-jag1-rbpj-signalling-promotes-inflammatory-leukocyte-recruitment-and-atherosclerosis
#14
Meritxell Nus, Beatriz Martínez-Poveda, Donal MacGrogan, Rafael Chevre, Gaetano D'Amato, Mauro Sbroggio, Cristina Rodríguez, José Martínez-González, Vicente Andrés, Andrés Hidalgo, José Luis de la Pompa
AIMS: To determine the role of NOTCH during the arterial injury response and the subsequent chronic arterial-wall inflammation underlying atherosclerosis. METHODS AND RESULTS: We have generated a mouse model of endothelial-specific (Cdh5-driven) depletion of the Notch effector RBPJ (ApoE(-/-);RBPJ(flox/flox);Cdh5-Cre(ERT)). Endothelial-specific deletion of RBPJ or systemic deletion of Notch1 in athero-susceptible ApoE(-/-) mice fed a high cholesterol diet for 6 weeks resulted in reduced atherosclerosis in the aortic arch and sinus...
August 5, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27466498/protein-bound-polysaccharide-k-inhibits-hedgehog-signaling-through-down-regulation-of-maml3-and-rbpj-transcription-under-hypoxia-suppressing-the-malignant-phenotype-in-pancreatic-cancer
#15
Akio Yamasaki, Hideya Onishi, Akira Imaizumi, Makoto Kawamoto, Akiko Fujimura, Yasuhiro Oyama, Mitsuo Katano
Hedgehog signaling is activated in pancreatic cancer and could be a therapeutic target. We previously demonstrated that recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) contribute to the hypoxia-induced up-regulation of Smoothened (SMO) transcription. We have also shown that protein-bound polysaccharide-K (PSK) could be effective for refractory pancreatic cancer that down-regulates SMO transcription under hypoxia. In this study, we evaluated whether the anticancer mechanism of PSK involves inhibiting RBPJ and MAML3 expression under hypoxia...
August 2016: Anticancer Research
https://www.readbyqxmd.com/read/27427944/correction-rbpj-the-major-transcriptional-effector-of-notch-signaling-remains-associated-with-chromatin-throughout-mitosis-suggesting-a-role-in-mitotic-bookmarking
#16
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pgen.1004204.].
July 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27426040/reciprocal-regulation-between-bifunctional-mir-9-9-%C3%A2-and-its-transcriptional-modulator-notch-in-human-neural-stem-cell-self-renewal-and-differentiation
#17
Beate Roese-Koerner, Laura Stappert, Thomas Berger, Nils Christian Braun, Monika Veltel, Johannes Jungverdorben, Bernd O Evert, Michael Peitz, Lodovica Borghese, Oliver Brüstle
Tight regulation of the balance between self-renewal and differentiation of neural stem cells is crucial to assure proper neural development. In this context, Notch signaling is a well-known promoter of stemness. In contrast, the bifunctional brain-enriched microRNA miR-9/9(∗) has been implicated in promoting neuronal differentiation. Therefore, we set out to explore the role of both regulators in human neural stem cells. We found that miR-9/9(∗) decreases Notch activity by targeting NOTCH2 and HES1, resulting in an enhanced differentiation...
August 9, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27369045/rbpj-may-be-a-more-effective-therapeutic-target-than-notch-in-gbm
#18
(no author information available yet)
RBPJ is required for GBM tumor-initiating cell self-renewal and tumor growth.
August 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27362333/endothelial-notch-signaling-is-essential-to-prevent-hepatic-vascular-malformations-in-mice
#19
Henar Cuervo, Corinne M Nielsen, Douglas A Simonetto, Linda Ferrell, Vijay H Shah, Rong A Wang
UNLABELLED: Liver vasculature is crucial for adequate hepatic functions. Global deletion of Notch signaling in mice results in liver vascular pathologies. However, whether Notch in endothelium is essential for hepatic vascular structure and function remains unknown. To uncover the function of endothelial Notch in the liver, we deleted Rbpj, a transcription factor mediating all canonical Notch signaling, or Notch1 from the endothelium of postnatal mice. We investigated the hepatic vascular defects in these mutants...
October 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27357444/notch-independent-rbpj-controls-angiogenesis-in-the-adult-heart
#20
Ramón Díaz-Trelles, Maria Cecilia Scimia, Paul Bushway, Danh Tran, Anna Monosov, Edward Monosov, Kirk Peterson, Stacey Rentschler, Pedro Cabrales, Pilar Ruiz-Lozano, Mark Mercola
Increasing angiogenesis has long been considered a therapeutic target for improving heart function after injury such as acute myocardial infarction. However, gene, protein and cell therapies to increase microvascularization have not been successful, most likely because the studies failed to achieve regulated and concerted expression of pro-angiogenic and angiostatic factors needed to produce functional microvasculature. Here, we report that the transcription factor RBPJ is a homoeostatic repressor of multiple pro-angiogenic and angiostatic factor genes in cardiomyocytes...
June 30, 2016: Nature Communications
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