RT Journal Article
SR Electronic
T1 Fas Preassociation Required for Apoptosis Signaling and Dominant Inhibition by Pathogenic Mutations
JF Science
JO Science
FD American Association for the Advancement of Science
SP 2354
OP 2357
DO 10.1126/science.288.5475.2354
VO 288
IS 5475
A1 Siegel, Richard M.
A1 Frederiksen, John K.
A1 Zacharias, David A.
A1 Chan, Francis Ka-Ming
A1 Johnson, Michele
A1 Lynch, David
A1 Tsien, Roger Y.
A1 Lenardo, Michael J.
YR 2000
UL http://science.sciencemag.org/content/288/5475/2354.abstract
AB Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerization, was found to stem from ligand- independent interaction of wild-type and mutant Fas receptors through a specific region in the extracellular domain. Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein. These results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.