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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-1-10
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pubmed:abstractText |
Apoptosis signaling through CD95 (Fas/APO-1) involves aggregation and clustering of the receptor followed by its actin-dependent internalization. Internalization is required for efficient formation of the death-inducing signaling complex (DISC) with maximal recruitment of FADD, caspase-8/10 and c-FLIP occurring when the receptor has reached an endosomal compartment. The first detectable event during CD95 signaling is the formation of SDS-stable aggregates likely reflecting intense oligomerization of the receptor. We now demonstrate that these SDS-stable forms of CD95 correspond to very high molecular weight DISC complexes (hiDISC) and are the sites of caspase-8 activation. hiDISCs are found both inside and outside of detergent-resistant membranes. The formation of SDS-stable CD95 aggregates involves palmitoylation of the membrane proximal cysteine 199 in CD95. Cysteine 199 mutants no longer form SDS-stable aggregates, and inhibition of palmitoylation reduces internalization of CD95 and activation of caspase-8. Our data demonstrate that SDS-stable forms of CD95 are the sites of apoptosis initiation and represent an important early step in apoptosis signaling through CD95 before activation of caspases.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-10608899,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-10875918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-11287428,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-11418635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-11733517,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-11739735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-11818332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-12110583,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-12620239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-12655293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-12832037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-12934106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-14563117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-14634070,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-14745445,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-15163537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-15189153,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-15214041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-15272306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-15313558,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-15557123,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-15795317,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-16009715,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-16393952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-16498403,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-2787530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-8413237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-8521815,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-8681377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-8690074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-9184224,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-9268381,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-9341131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-9485186,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-9501089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-9727491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-9727492,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-9880531,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159907-9950028
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/CFLAR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 10,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Cflar protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Palmitic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Dodecyl Sulfate
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
221-31
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17159907-Amino Acid Sequence,
pubmed-meshheading:17159907-Animals,
pubmed-meshheading:17159907-Antigens, CD95,
pubmed-meshheading:17159907-Apoptosis,
pubmed-meshheading:17159907-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:17159907-Caspase 10,
pubmed-meshheading:17159907-Caspase 8,
pubmed-meshheading:17159907-Endosomes,
pubmed-meshheading:17159907-Humans,
pubmed-meshheading:17159907-Mice,
pubmed-meshheading:17159907-Molecular Sequence Data,
pubmed-meshheading:17159907-Palmitic Acids,
pubmed-meshheading:17159907-Signal Transduction,
pubmed-meshheading:17159907-Sodium Dodecyl Sulfate
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pubmed:year |
2007
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pubmed:articleTitle |
Palmitoylation of CD95 facilitates formation of SDS-stable receptor aggregates that initiate apoptosis signaling.
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pubmed:affiliation |
The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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