JBC Transcription and Nuclear Factor Monoclonals

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Papers In Press, published online ahead of print July 5, 2000
J. Biol. Chem, 10.1074/jbc.M005214200
Submitted on June 15, 2000
Revised on July 3, 2000
Accepted on July 5, 2000

Chopper, a new death domain of the p75 neurotrophin receptor that mediates rapid neuronal cell death

Elizabeth J. Coulson, Kate Reid, Manuel Baca, Kylie A. Shipham, Sarah M. Hulett, Trevor J. Kilpatrick, and Perry F. Bartlett

Neurobiology and Development, Walter and Eliza Hall Institute, Parkville, Victoria 3050

Corresponding Author: coulson{at}wehi.edu.au

The cytoplasmic juxtamembrane region of the p75 neurotrophin receptor (p75NTR) has been found to be necessary and sufficient to initiate neural cell death. The region was named 'Chopper' to distinguish it from CD95-like death domains. A 29 amino acid peptide corresponding to the Chopper region induced caspase- and calpain-mediated death in a variety of neural and non-neural cell types, and was not inhibited by signaling through Trk (unlike killing by full-length p75NTR). Chopper triggered cell death only when bound to the plasma membrane by a lipid anchor, whereas non-anchored Chopper acted in a dominant-negative manner blocking p75NTR-mediated death both in vitro and in vivo. Removal of the ectodomain of p75NTR increased the potency of Chopper activity suggesting it regulated association of Chopper with downstream signaling proteins.


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