Arbiter of differentiation and death: Notch signaling meets apoptosis

J Cell Physiol. 1999 Dec;181(3):393-409. doi: 10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6.


Notch-ligand interactions are a highly conserved mechanism that regulates cell fate decisions. Over the past few years, numerous observations have shown that this mechanism operates to regulate cell differentiation in an enormous variety of developmental and cell maturation processes. Recent studies indicate that in addition to cell differentiation, Notch signaling has direct effects on proliferation and programmed cell death. The picture emerging from these findings suggests that, depending on cellular and developmental context, Notch signaling may function as a general "arbiter" of cell fate, regulating differentiation potential, rate of proliferation, and apoptotic cell death. In this review, we briefly summarize the current knowledge of the structure and function of Notch receptors and discuss the recent evidence that Notch signaling regulates apoptotic cell death. The possible mechanisms of this effect and its potential implications for developmental biology, immunobiology, neuropathology, and tumor biology are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / etiology
  • Animals
  • Apoptosis / physiology*
  • Cell Differentiation / physiology*
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Models, Biological
  • Neoplasms / pathology
  • Neoplasms / physiopathology
  • Neoplasms / therapy
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology
  • Receptors, Notch
  • Signal Transduction
  • Thymus Gland / cytology
  • Thymus Gland / growth & development
  • Transcription Factors / physiology


  • Membrane Proteins
  • Receptors, Cell Surface
  • Receptors, Notch
  • Transcription Factors