Although TRAIL does not seem to be required for the activation of Bim, TRAIL synergizes with paracetamol in activating Bid most likely via induction of caspase 8 activation and subsequent processing of Bid.
Activated BID does not activate WT BOK or the stabilized alanine mutant to promote cell death.
In certain cell types, cathepsins and/or chymotrypsin rapidly process and thereby activate Bid in the cytosol, which in turn triggers MOMP and results in mitochondria-dependent apoptosis (Zhao et al., 2010; Zhao et al., 2012).
CCCP treatment, or CD95 triggering, which involves activated Bid [ 42], was unaffected (Fig. 7b).
The tumor suppressor p53 has been shown to bind to the Bid promoter p53-responsive sequence and activate Bid transcription.
Activated Bid can antagonize Bcl-2, and may thus overcome the Bcl-2-mediated antiapoptotic barrier in melanoma cells.
Further, Gra-B can mediate apoptosis independent of caspases, or by directly activating caspases or indirectly by activating Bid [ 148, 149].
In our hands, neither caspase-8 nor activated Bid alone permeabilized the membrane of isolated lysosomes [ 26], suggesting that additional factors, such as Bax or Bak, are indeed required.
However, coexposure to BH3 mimetic compounds (such as HA14-1 and ABT-737) could potentially displacouldtivated Bid from Bcl-2, and thus potentiallyl displace
Thus, lpr mice may also have less apoptotic cells over time due to an inability to activate Bid and the apoptotic cascade.
