p75NTR and the concept of cellular dependence: seeing how the other half die - PubMed (original) (raw)
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p75NTR and the concept of cellular dependence: seeing how the other half die
D E Bredesen et al. Cell Death Differ. 1998 May.
Abstract
Cells depend on specific stimuli, such as trophic factors, for survival and in the absence of such stimuli, undergo apoptosis. How do cells initiate apoptosis in response to the withdrawal of trophic factors or other dependent stimuli? Recent studies of apoptosis induction by neurotrophin withdrawal argue for a novel form of pro-apoptotic signal transduction - 'negative signal transduction' - in which the absence of ligand-receptor interaction induces cell death. We have found that the prototype for this form of signaling - the common neurotrophin receptor, p75NTR - creates a state of cellular dependence (or addiction) on neurotrophins, and that this effect requires an 'addiction/dependence domain' (ADD) in the intracytoplasmic region of p75NTR. We have recently found other receptors that include dependence domains, arguing that dependence receptors, and their associated dependence domains, may be involved in a rather general mechanism to create cellular states of dependence on trophic factors, cytokines, adhesion, electrical activity and other dependent stimuli.
Comment in
- Life and death decisions: a biological role for the p75 neurotrophin receptor.
Miller FD, Kaplan DR. Miller FD, et al. Cell Death Differ. 1998 May;5(5):343-5. doi: 10.1038/sj.cdd.4400385. Cell Death Differ. 1998. PMID: 10200482 No abstract available.
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