title: The intracellular domain of Notch ligand Delta1 induces cell growth arrest.
abstract: Notch signaling involves proteolytic cleavage of the transmembrane Notch receptor after binding to its transmembrane ligands, Delta or Jagged; and the resultant soluble intracellular domain of Notch stimulates a cascade of transcriptional events. The Delta1 ligand also undergoes proteolytic cleavage upon Notch binding, resulting in the production of a free intracellular domain. We demonstrate that the expression of the intracellular domain of Delta1 results in a non-proliferating senescent-like cell phenotype which is dependent on the expression of the cell cycle inhibitor, p21, and is abolished by co-expression of constitutively active Notch1. These data suggest a new intracellular role for Delta1.
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, 04074, USA.
authors.forename: Vihren
authors.initials: V
authors.lastname: Kolev
authors.forename: Doreen
authors.initials: D
authors.lastname: Kacer
authors.forename: Radianna
authors.initials: R
authors.lastname: Trifonova
authors.forename: Deena
authors.initials: D
authors.lastname: Small
authors.forename: Maria
authors.initials: M
authors.lastname: Duarte
authors.forename: Raffaella
authors.initials: R
authors.lastname: Soldi
authors.forename: Irene
authors.initials: I
authors.lastname: Graziani
authors.forename: Olga
authors.initials: O
authors.lastname: Sideleva
authors.forename: Barry
authors.initials: B
authors.lastname: Larman
authors.forename: Thomas
authors.initials: T
authors.lastname: Maciag
authors.forename: Igor
authors.initials: I
authors.lastname: Prudovsky
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016922:Cellular Senescence; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; C064045:delta protein