, Volume 9, Issue 1, pp 37–49

The dependence receptor hypothesis

  • P. Mehlen
  • D. E. Bredesen

DOI: 10.1023/B:APPT.0000012120.66221.b2

Cite this article as:
Mehlen, P. & Bredesen, D.E. Apoptosis (2004) 9: 37. doi:10.1023/B:APPT.0000012120.66221.b2


A new family of functionally-related receptors has recently been proposed, dubbed dependence receptors. These proteins, only some of which share sequence similarities, display the common property that they transduce two different intracellular signals: in the presence of ligand, these receptors transduce a positive signal leading to survival, differentiation or migration; conversely, in the absence of ligand, the receptors initiate or amplify a signal for programmed cell death. Thus cells that express these proteins at sufficient concentrations manifest a state of dependence on their respective ligands. The signaling that mediates cell death induction upon ligand withdrawal is in large part uncharacterized, but typically includes a required interaction with, and cleavage by, specific caspases. Here, we review the current knowledge concerning dependence receptors, including the shared mechanisms for cell death induction and their potential relevance in nervous system development and regulation of tumorigenesis.

apoptosis carpase dependence receptor nervous system tumorigenesis 

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • P. Mehlen
    • 1
  • D. E. Bredesen
    • 2
    • 3
  1. 1.Apoptosis/Differentiation Laboratory, Equipe labelisée ‘La Ligue’, Molecular and Cellular Genetic Center, CNRS UMR 5534University of LyonVilleurbanneFrance
  2. 2.The Buck Institute for Age ResearchNovatoUSA;
  3. 3.University of California, San FranciscoSan FranciscoUSA