Abstract The apoptosome is a multimolecular complex assembled around the adaptor protein Apaf1 upon mitochondria-mediated apoptosis. The formation of the apoptosome needs the presence of ATP/dATP and cytochrome c in the cytosol and triggers the activation of caspases which – in turn – drive cell demise. Apoptosis plays a key role in the homeostasis of all multicellular organisms and, indeed, wi...

How Bcl-2 and its pro-survival relatives prevent activation of the caspases that mediate apoptosis is unknown, but they appear to act through the caspase activator apoptosis protease-activating factor 1 (Apaf-1). According to the apoptosome model, the Bcl-2-like proteins preclude Apaf-1 activity by sequestering the protein. To explore Apaf-1 function and to test this model, we generated monoclo...

In chronic myeloid leukemia (CML) proliferation is increased and resistance to apoptosis has been proposed as a mechanism accounting for myeloid cell expansion. There is still controversy on whether apoptosis plays an important role in the regulation of myelopoiesis. This study aims to investigate whether apoptosis-related proteins play a role in the evolution of CML and to identify, the relati...

The Apaf-1 apoptosome is a multi-subunit caspase-activating scaffold that is assembled in response to diverse forms of cellular stress that culminate in apoptosis. To date, most studies on apoptosome composition and function have used apoptosomes reassembled from recombinant or purified proteins. Thus, the precise composition of native apoptosomes remains unresolved. Here, we have used a one-st...

According to dogma, initiator caspases are activated through proximity-induced homodimerization, but some studies infer that during apoptosis caspase-9 may instead form a holoenzyme with the Apaf-1 apoptosome. Using several biochemical approaches, including a novel site-specific crosslinking technique, we provide the first direct evidence that procaspase-9 homodimerizes within the apoptosome, m...