TGFβ-mediated apoptosis of Burkitt's lymphoma BL41 cells is associated with the relocation of mitochondrial BimEL

Caspase-3 triggers a TPCK-sensitive protease pathway leading to degradation of the BH3-only protein puma

“…1e). Interestingly, these proteins have been shown to be subject to caspasemediated cleavage [17][18][19] and, as the stimuli used here also induce caspase activation [20][21][22][23], we decided to test the hypothesis that this Puma downregulation was dependent on caspase activation.…”

Mcl‐1128–350 fragment induces apoptosis through direct interaction with Bax

“…Collectively, our data support a model in which Mcl‐1 128–350 exerts a pro‐apoptotic function in very different cell types governed by its capacity to interact physically with Bax. Mcl‐1 cleavage appears to be associated with very different pro‐apoptotic stimuli (chemotherapy [7–9], inhibition of proteasome [20], death receptor signaling [21] and cytokine deprivation [22]) and occurs very early, suggesting a role of Mcl‐1 128–350 as both an inducer and an amplifier of apoptosis. Based on this study, we can propose that this cleaved fragment has an active role in mitochondrial perturbation via direct activation of Bax.…”

“…Both, proteasomal and caspase‐mediated cleavages of Mcl‐1 1–350 contribute to Mcl‐1 down‐regulation in response to signals that trigger cell death [5]. Mcl‐1 cleavage was first observed during Fas‐mediated apoptosis in Jurkat T cells [6] then associated with chemotherapy‐induced apoptosis in diverse cancer cells [7–9]. Mcl‐1 1–350 can be cleaved at two different sites (Asp 127 and Asp 157) by caspases, specifically caspase‐3, but it is thought, that the Mcl‐1 128–350 (Asp 127) cleavage product is the predominant form in apoptotic cells [10].…”

TGFβ and Bim: Partners in cell death

“…Interestingly, caspase-cleaved Bim EL exhibited increased binding to Bcl-2 and therefore increased apoptotic potency relative to full-length Bim EL . Recently, a role for TGFβ in both caspase activation and Bim relocation has been demonstrated in Burkitt's lymphoma cells (Clybouw et al, 2008;Schrantz et al, 2001). TGFβ triggered a p38-dependent activation of caspase 8, which cleaved the pro-survival protein Mcl-1.…”