Fig. 5
From: Complex and pleiotropic signaling pathways regulated by the secreted protein augurin
Augurin-mediated regulation of apoptotic signaling pathways. The activation of the FAS receptor induces the cleavage of procaspase 8 into caspase 8, which in turn induces the cleavage of procaspase 3 into caspase 3, finally leading to cell death. Caspase 8 can also promote the cleavage of BID, which is a pro-apoptotic molecule that induces Bax/Bak assembly, outer mitochondria membrane permeabilization and cytochrome c release, triggering the mitochondrial apoptotic pathway. Bcl2 is an anti-apoptotic factor which counteracts those actions. Augurin negatively regulates Fas-induced apoptosis in human T-leukemia cells by associating to procaspase 8 and preventing its cleavage to caspase 8 and consequently BID cleavage [50] (left panel). In other cellular models augurin seems to play a pro-apoptotic function increasing the expression levels of cleaved-PARP, cleaved-caspase-3 and Bax, while decreasing the expression levels of the anti-apoptotic factor Bcl2 (right panel), all those actions stimulating the mitochondrial apoptotic pathway [27, 32, 51]