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. Author manuscript; available in PMC: 2005 Sep 6.
Published in final edited form as: Leuk Lymphoma. 2003 Jul;44(7):1209–1214. doi: 10.1080/1042819031000068052

FIGURE 1.

FIGURE 1

Model for activation of apoptosis in MM by IFNs. Following transcriptional induction by IFNs, Apo2L engages its receptor DR5 (or DR4) and, through an adaptor intermediate (FADD), recruits caspase 8 to the cell membrane. A similar pathway is activated by the trimeric Apo2L/TRAIL prepared for clinical studies [17]. Following caspase 8 activation by proteolysis, Bid is cleaved and translocates to mitochondria, causing release of low levels of cytochrome c into the cytosol, leading to caspase 9 and 3 activation. This results in attack of the anti-apoptotic protein Bcl-2 on the mitochondrial membranes, producing a truncated Bcl-2Δ protein, which causes release of more cyt c, caspase activation, and apoptosis. Bcl-xL transcriptional down-regulation is an additional mechanism by which IFNs may decrease levels of anti-apoptotic proteins shifting the balance towards a pro-apoptotic state (modified from Ref. [4], with permission).