Dimer‐specific immunoprecipitation of active caspase‐2 identifies TRAF proteins as novel activators
Abstract: Caspase‐2 has been shown to initiate apoptotic cell death in response to specific intracellular stressors such as DNA damage. However, the molecular mechanisms immediately upstream of its activation are still poorly understood. We combined a caspase‐2 bimolecular fluorescence complementation (BiFC) system with fluorophore‐specific immunoprecipitation to isolate and study the active caspase‐2 dimer and its interactome. Using this technique, we found that tumor necrosis factor receptor‐associated factor 2 (TRAF2), as well as TRAF1 and 3, directly binds to the active caspase‐2 dimer. TRAF2 in particular is necessary for caspase‐2 activation in response to apoptotic cell death stimuli. Furthermore, we found that dimerized caspase‐2 is ubiquitylated in a TRAF2‐dependent manner at K15, K152, and K153, which in turn stabilizes the active caspase‐2 dimer complex, promotes its association with an insoluble cellular fraction, and enhances its activity to fully commit the cell to apoptosis. Together, these data indicate that TRAF2 positively regulates caspase‐2 activation and consequent cell death by driving its activation through dimer‐stabilizing ubiquitylation.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Dimer‐specific immunoprecipitation of active caspase‐2 identifies TRAF proteins as novel activators ; volume:37 ; number:14 ; year:2018 ; extent:20
The EMBO journal / European Molecular Biology Organization ; 37, Heft 14 (2018) (gesamt 20)
- Urheber
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Robeson, Alexander C.
Lindblom, Kelly R.
Wojton, Jeffrey
Kornbluth, Sally
Matsuura, Kenkyo
- DOI
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10.15252/embj.201797072
- URN
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urn:nbn:de:101:1-2022090820365858556756
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.0001, 06:37 MEZ
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Beteiligte
- Robeson, Alexander C.
- Lindblom, Kelly R.
- Wojton, Jeffrey
- Kornbluth, Sally
- Matsuura, Kenkyo
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