The intracellular domain of Notch ligand Delta1 induces cell growth arrest.
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.
Kolev
Vihren
V
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, 04074, USA.
Kacer
Doreen
D
Trifonova
Radianna
R
Small
Deena
D
Duarte
Maria
M
Soldi
Raffaella
R
Graziani
Irene
I
Sideleva
Olga
O
Larman
Barry
B
Maciag
Thomas
T
Prudovsky
Igor
I
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
D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; C064045:delta protein