The intracellular domain of Notch ligand Delta1 induces cell growth arrest

  • Kolev V
  • Kacer D
  • Trifonova R
 et al. 
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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.

Author-supplied keywords

  • *Cell Proliferation
  • Animals
  • Cell Aging
  • Humans
  • Ligands
  • Membrane Proteins/chemistry/genetics/*metabolism
  • Mice
  • NIH 3T3 Cells
  • Protein Structure, Tertiary
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

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Authors

  • V Kolev

  • D Kacer

  • R Trifonova

  • D Small

  • M Duarte

  • R Soldi

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