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© The Rockefeller University Press, 0021-9525/1998//1243 $5.00
The Journal of Cell Biology, Volume 141, Number 5, , 1998 1243-1253


Articles

Death-effector Filaments: Novel Cytoplasmic Structures that Recruit Caspases and Trigger Apoptosis



Richard M. Siegel*, David A. Martin*, Lixin Zheng*, Samuel Y. Ng*, John Bertin{ddagger}, Jeffrey Cohen{ddagger}, and Michael J. Lenardo*

* Laboratory of Immunology and {ddagger} Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

The death-effector domain (DED) is a critical protein interaction domain that recruits caspases into complexes with members of the TNF-receptor superfamily. Apoptosis can also be induced by expressing certain DED-containing proteins without surface receptor cross-linking. Using Green Fluorescent Protein to examine DED-containing proteins in living cells, we show that these proteins cause apoptosis by forming novel cytoplasmic filaments that recruit and activate pro-caspase zymogens. Formation of these filaments, which we term death-effector filaments, was blocked by coexpression of viral antiapoptotic DED-containing proteins, but not by bcl-2 family proteins. Thus, formation of death-effector filaments allows a regulated intracellular assembly of apoptosis-signaling complexes that can initiate or amplify apoptotic stimuli independently of receptors at the plasma membrane.


Abbreviations used in this paper: DED, death-effector domain; DEF, death-effector filaments; FLIP, FLICE (caspase-8) inhibitory proteins; inhibitory proteins, GFP, green fluorescent protein; v-FLIP, viral DED-containing proteins.

D.A. Martin was a research scholar with the Howard Hughes Medical Institute.

The present address of John Bertin is Millennium Pharmaceuticals, 640 Memorial Drive, Cambridge, MA 02139.

Address all correspondence to Michael J. Lenardo, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N311, Bethesda, MD 20892. E-mail: mlenardo{at}atlas.niaid.nih.gov



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