Co-operative and hierarchical binding of c-FLIP and caspase-8: a unified model defines how c-FLIP isoforms differentially control cell fate
The death-inducing signaling complex (DISC) initiates death receptor-induced apoptosis. DISC assembly and activation are controlled by c-FLIP isoforms, which function as pro-apoptotic (c-FLIPL only) or anti-apoptotic (c-FLIPL/c-FLIPS) regulators of procaspase-8 activation. Current models assume that...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 17, 2016
|
| In: |
Molecular cell
Year: 2016, Volume: 61, Issue: 6, Pages: 834-849 |
| ISSN: | 1097-4164 |
| DOI: | 10.1016/j.molcel.2016.02.023 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.molcel.2016.02.023 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1097276516001349 
|
| Author Notes: | Michelle A. Hughes, Ian R. Powley, Rebekah Jukes-Jones, Sebastian Horn, Maria Feoktistova, Louise Fairall, John W.R. Schwabe, Martin Leverkus, Kelvin Cain, and Marion MacFarlane |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1588186881 | ||
| 003 | DE-627 | ||
| 005 | 20250206101010.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190227s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.molcel.2016.02.023 |2 doi | |
| 035 | |a (DE-627)1588186881 | ||
| 035 | |a (DE-576)518186881 | ||
| 035 | |a (DE-599)BSZ518186881 | ||
| 035 | |a (OCoLC)1341040562 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Hughes, Michelle A. |e VerfasserIn |0 (DE-588)1179301374 |0 (DE-627)1066801797 |0 (DE-576)518184404 |4 aut | |
| 245 | 1 | 0 | |a Co-operative and hierarchical binding of c-FLIP and caspase-8 |b a unified model defines how c-FLIP isoforms differentially control cell fate |c Michelle A. Hughes, Ian R. Powley, Rebekah Jukes-Jones, Sebastian Horn, Maria Feoktistova, Louise Fairall, John W.R. Schwabe, Martin Leverkus, Kelvin Cain, and Marion MacFarlane |
| 264 | 1 | |c March 17, 2016 | |
| 300 | |a 16 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 27.02.2019 | ||
| 520 | |a The death-inducing signaling complex (DISC) initiates death receptor-induced apoptosis. DISC assembly and activation are controlled by c-FLIP isoforms, which function as pro-apoptotic (c-FLIPL only) or anti-apoptotic (c-FLIPL/c-FLIPS) regulators of procaspase-8 activation. Current models assume that c-FLIP directly competes with procaspase-8 for recruitment to FADD. Using a functional reconstituted DISC, structure-guided mutagenesis, and quantitative LC-MS/MS, we show that c-FLIPL/S binding to the DISC is instead a co-operative procaspase-8-dependent process. FADD initially recruits procaspase-8, which in turn recruits and heterodimerizes with c-FLIPL/S via a hierarchical binding mechanism. Procaspase-8 activation is regulated by the ratio of unbound c-FLIPL/S to procaspase-8, which determines composition of the procaspase-8:c-FLIPL/S heterodimer. Thus, procaspase-8:c-FLIPL exhibits localized enzymatic activity and is preferentially an activator, promoting DED-mediated procaspase-8 oligomer assembly, whereas procaspase-8:c-FLIPS lacks activity and potently blocks procaspase-8 activation. This co-operative hierarchical binding model explains the dual role of c-FLIPL and crucially defines how c-FLIP isoforms differentially control cell fate. | ||
| 700 | 1 | |a Horn, Sebastian |e VerfasserIn |0 (DE-588)105602805X |0 (DE-627)793165040 |0 (DE-576)412042630 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular cell |d [Cambridge, Mass.] : Cell Press, 1997 |g 61(2016), 6, Seite 834-849 |h Online-Ressource |w (DE-627)320416097 |w (DE-600)2001948-8 |w (DE-576)090881362 |x 1097-4164 |7 nnas |a Co-operative and hierarchical binding of c-FLIP and caspase-8 a unified model defines how c-FLIP isoforms differentially control cell fate |
| 773 | 1 | 8 | |g volume:61 |g year:2016 |g number:6 |g pages:834-849 |g extent:16 |a Co-operative and hierarchical binding of c-FLIP and caspase-8 a unified model defines how c-FLIP isoforms differentially control cell fate |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.molcel.2016.02.023 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u http://www.sciencedirect.com/science/article/pii/S1097276516001349 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190227 | ||
| 993 | |a Article | ||
| 994 | |a 2016 | ||
| 998 | |g 105602805X |a Horn, Sebastian |m 105602805X:Horn, Sebastian |d 60000 |d 61900 |e 60000PH105602805X |e 61900PH105602805X |k 0/60000/ |k 1/60000/61900/ |p 4 | ||
| 999 | |a KXP-PPN1588186881 |e 3056856930 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"family":"Hughes","given":"Michelle A.","display":"Hughes, Michelle A.","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Horn","given":"Sebastian","display":"Horn, Sebastian","roleDisplay":"VerfasserIn","role":"aut"}],"title":[{"title_sort":"Co-operative and hierarchical binding of c-FLIP and caspase-8","title":"Co-operative and hierarchical binding of c-FLIP and caspase-8","subtitle":"a unified model defines how c-FLIP isoforms differentially control cell fate"}],"language":["eng"],"recId":"1588186881","type":{"media":"Online-Ressource","bibl":"article-journal"},"note":["Gesehen am 27.02.2019"],"name":{"displayForm":["Michelle A. Hughes, Ian R. Powley, Rebekah Jukes-Jones, Sebastian Horn, Maria Feoktistova, Louise Fairall, John W.R. Schwabe, Martin Leverkus, Kelvin Cain, and Marion MacFarlane"]},"id":{"doi":["10.1016/j.molcel.2016.02.023"],"eki":["1588186881"]},"origin":[{"dateIssuedDisp":"March 17, 2016","dateIssuedKey":"2016"}],"relHost":[{"id":{"issn":["1097-4164"],"eki":["320416097"],"zdb":["2001948-8"]},"origin":[{"dateIssuedKey":"1997","publisher":"Cell Press ; Elsevier","dateIssuedDisp":"1997-","publisherPlace":"[Cambridge, Mass.] ; New York, NY"}],"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title_sort":"Molecular cell","title":"Molecular cell"}],"language":["eng"],"recId":"320416097","type":{"media":"Online-Ressource","bibl":"periodical"},"note":["Gesehen am 01.08.25"],"disp":"Co-operative and hierarchical binding of c-FLIP and caspase-8 a unified model defines how c-FLIP isoforms differentially control cell fateMolecular cell","part":{"volume":"61","text":"61(2016), 6, Seite 834-849","extent":"16","year":"2016","issue":"6","pages":"834-849"},"pubHistory":["1.1997/98 -"]}],"physDesc":[{"extent":"16 S."}]} | ||
| SRT | |a HUGHESMICHCOOPERATIV1720 | ||