Identification of Components of the Cell Death Pathway
Abstract
The inability of wt-Huntington expressed in C. elegans indicates that its anti-apoptotic function affects non-conserved aspects of Caspase-9 activation. We established a cellular model for the apoptotic signaling of p75NTR The conditionally immortalized neuronal cells used is the first system in which p75NTR induces apoptosis in the absence of any co-stimuli. The tools are now in hand to identify the intracellular signaling components involved in transmitting the apoptotic signal from this receptor. A close homologue of p75NTR, NRADD, was also characterized. Despite its close homology, NRADD signals apoptosis by a different mechanism. Its activity is controlled by N-glycosylation and dominant negative constructs interfere with apoptotie stimuli generated at the endoplasmatic reticulum. Transgenic expression of the viral PAN-death receptor inhibitor ES protected mice from excitatory damage induced by kainic acid. This observation is highly relevant for neurodegenerative diseases like multiple sclerosis where excitatory and immune mediated damage is observed. New insight into the assembly of death domain complexes was obtained by analyzing published structures of death domains heterodimeres. It emerges that death domains can interact in such a way to mediate multivalent interactions and not only monovalent associations as currently thought.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA398498
Entities
People
- Claudius Vincenz
Organizations
- University of Michigan