title: Atrophin protein RERE positively regulates Notch targets in the developing vertebrate spinal cord.
abstract: The Notch signaling pathway controls cell fate decision, proliferation, and other biological functions in both vertebrates and invertebrates. Precise regulation of the canonical Notch pathway ensures robustness of the signal throughout development and adult tissue homeostasis. Aberrant Notch signaling results in profound developmental defects and is linked to many human diseases. In this study, we identified the Atrophin family protein RERE (also called Atro2) as a positive regulator of Notch target Hes genes in the developing vertebrate spinal cord. Prior studies have shown that during early embryogenesis in mouse and zebrafish, deficit of RERE causes various patterning defects in multiple organs including the neural tube. Here, we detected the expression of RERE in the developing chick spinal cord, and found that normal RERE activity is needed for proper neural progenitor proliferation and neuronal differentiation possibly by affecting Notch-mediated Hes expression. In mammalian cells, RERE co-immunoprecipitates with CBF1 and Notch intracellular domain (NICD), and is recruited to nuclear foci formed by over-expressed NICD1. RERE is also necessary for NICD to activate the expression of Notch target genes. Our findings suggest that RERE stimulates Notch target gene expression by preventing degradation of NICD protein, thereby facilitating the assembly of a transcriptional activating complex containing NICD, CBF1/RBPjκ in vertebrate, Su(H) in Drosophila melanogaster, Lag1 in C. elegans, and other coactivators.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China.|Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School of Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Hui
authors.identifier: 0000-0002-5444-1579
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School of Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Gui
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School of Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rallo
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School of Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Matise
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002642:Chick Embryo; D018274:Electroporation; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D058953:Neural Stem Cells; D009474:Neurons; D051880:Receptors, Notch / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D051880:Receptors, Notch
keywords: 
  NICD
  ; 
  RERE
  ; Atrophin; CBF1; Notch