Low probability activation of Bax/Bak can induce selective killing of cancer cells by generating heterogeneity in apoptosis.

Biomimetic pro-apoptotic agents (e.g., BH3 mimetics) have been shown to activate the intrinsic death pathway (Type 2 apoptosis) selectively in cancer cells, a mechanism that can be key to developing successful anti-cancer therapy.

Formation of BCR oligomers provides a mechanism for B cell affinity discrimination.

B cells encounter antigen over a wide affinity range, from K(A)=10(5) M(-1) to K(A)=10(10) M(-1). The strength of B cell antigen receptor (BCR) signaling in response to antigen increases with affinity, a process known as "affinity discrimination". In this work, we use a computational simulation of B cell surface dynamics and membrane-proximal signaling to show that affinity discrimination can arise from the formation of BCR oligomers.

Discrimination of membrane antigen affinity by B cells requires dominance of kinetic proofreading over serial engagement.

B-cell receptor signaling in response to membrane-bound antigen increases with antigen affinity, a process known as affinity discrimination. We use computational modeling to show that B-cell affinity discrimination requires that kinetic proofreading predominate over serial engagement. We find that if B-cell receptors become signaling-capable immediately upon antigen binding, which results in decreasing serial engagement as affinity increases, then increasing affinity can lead to weaker signaling.

Nonlinear regulation of commitment to apoptosis by simultaneous inhibition of Bcl-2 and XIAP in leukemia and lymphoma cells.

Apoptosis is a complex pathway regulated by the concerted action of multiple pro- and anti-apoptotic molecules. The intrinsic (mitochondrial) pathway of apoptosis is governed up-stream of mitochondria, by the family of Bcl-2 proteins, and down-stream of mitochondria, by low-probability events, such as apoptosome formation, and by feedback circuits involving caspases and inhibitor of apoptosis proteins (IAPs), such as XIAP. All these regulatory mechanisms ensure that cells only commit to death once a threshold of damage has been reached and the anti-apoptotic reserve of the cell is overcome.