Drosophila Brat and Human Ortholog TRIM3 Maintain Stem Cell Equilibrium and Suppress Brain Tumorigenesis by Attenuating Notch Nuclear Transport

Cancer Research
Subhas MukherjeeDaniel J Brat

Abstract

Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. Mutation of a single gene in Drosophila, Brain Tumor (Brat), leads to disrupted asymmetric cell division resulting in dramatic neoplastic proliferation of neuroblasts and massive larval brain overgrowth. To uncover the mechanisms relevant to deregulated cell division in human glioma stem cells, we first developed a novel adult Drosophila brain tumor model using brat-RNAi driven by the neuroblast-specific promoter inscuteable Suppressing Brat in this population led to the accumulation of actively proliferating neuroblasts and a lethal brain tumor phenotype. brat-RNAi caused upregulation of Notch signaling, a node critical for self-renewal, by increasing protein expression and enhancing nuclear transport of Notch intracellular domain (NICD). In human glioblastoma, we demonstrated that the human ortholog of Drosophila Brat, tripartite motif-containing protein 3 (TRIM3), similarly suppressed NOTCH1 signaling and m...Continue Reading

References

Jul 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·P ZagourasS Artavanis-Tsakonas
May 11, 2000·Molecular and Cellular Biology·S Jeffries, A J Capobianco
Aug 27, 2002·Journal of Neurology·Jan J Heimans, Martin J B Taphoorn
May 3, 2005·Nature·Soo Jae LeeMurray Stewart
Sep 6, 2005·Nature Genetics·Emmanuel Caussinus, Cayetano Gonzalez
Apr 1, 2006·FEBS Letters·Anne Wilson, Freddy Radtke
Mar 21, 2007·Molecular and Cellular Biology·Motoshi NagaoMasato Nakafuku
Mar 18, 2008·Developmental Cell·Sarah K BowmanJuergen A Knoblich
Feb 13, 2010·Neuro-oncology·Marie-Thérése StockhausenHans Skovgaard Poulsen
May 11, 2010·Cellular and Molecular Life Sciences : CMLS·Kerstin HuennigerChristoph Kaether
Jun 11, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Prisca ChapoutonLaure Bally-Cuif
Sep 8, 2010·Current Topics in Developmental Biology·Jianing LiuAmy Wagers
Nov 26, 2010·Nature Reviews. Molecular Cell Biology·Juergen A Knoblich
Jul 23, 2011·Frontiers in Neuroanatomy·Miriam Matamales, Jean-Antoine Girault
Jan 24, 2012·Nature Cell Biology·Lydie CouturierFrançois Schweisguth
Jan 31, 2012·Seminars in Cell & Developmental Biology·Martin Baron
Jul 24, 2012·Current Opinion in Cell Biology·Vasundhara Kandachar, Fabrice Roegiers
Jan 31, 2013·Development·Ute KochFreddy Radtke
Nov 11, 2014·Stem Cells and Development·Subhas MukherjeeDaniel J Brat

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Citations

Jun 15, 2016·Trends in Pharmacological Sciences·Amarish Kumar YadavSubash Chandra Gupta
Jan 19, 2017·Molecular Oncology·Changming ZhangDaniel J Brat
Feb 2, 2017·The Journal of Clinical Investigation·Satoru Osuka, Erwin G Van Meir
Nov 29, 2017·Genes·Mariano Francesco CaratozzoloApollonia Tullo
May 24, 2019·Biological Chemistry·Felix Preston WilliamsJanosch Hennig
Nov 7, 2019·Stem Cells and Development·Valentina V Nenasheva, Vyacheslav Z Tarantul
Aug 2, 2020·Wiley Interdisciplinary Reviews. RNA·Robert P Connacher, Aaron C Goldstrohm
Mar 19, 2019·Frontiers in Genetics·Zhasmine MirzoyanPaola Bellosta
Aug 22, 2018·Journal of Developmental Biology·Eugenia C Olesnicky, Ethan G Wright
Feb 28, 2020·Cell Death & Disease·Josephine VolovetzJustin D Lathia
Jun 12, 2020·Genome Génome / Conseil National De Recherches Canada·Sophie E Keegan, Sarah C Hughes
Aug 22, 2018·G3 : Genes - Genomes - Genetics·Carin LoewenStanislava Chtarbanova
Nov 6, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Farhana AkterKhalid Shah
Dec 23, 2020·JCI Insight·Masahiro HitomiJustin D Lathia

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