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

SUBMITTER: Robeson AC 

PROVIDER: S-EPMC6043850 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature