Direct activation of full-length proapoptotic BAK.

Inactivation of prosurvival Bcl-2 proteins activates Bax/Bak through the outer mitochondrial membrane.

The mechanism of Bax/Bak activation remains a central question in mitochondria-dependent apoptotic signaling. While it is established that all proapoptotic Bcl-2 homology 3 (BH3)-only proteins bind and neutralize the anti-apoptotic Bcl-2 family proteins, how this neutralization leads to Bax/Bak activation has been actively debated. Here, genome editing was used to generate cells deficient for a...

Context-dependent Bcl-2/Bak interactions regulate lymphoid cell apoptosis.

The release of cytochrome c from mitochondria, which leads to activation of the intrinsic apoptotic pathway, is regulated by interactions of Bax and Bak with antiapoptotic Bcl-2 family members. The factors that regulate these interactions are, at the present time, incompletely understood. Recent studies showing preferences in binding between synthetic Bcl-2 homology domain 3 and antiapoptotic B...

Inhibits Bak Activation with the Proapoptotic Protein Bak and The Vaccinia Virus F1L Protein Interacts

The phosphorylation of Metaxin 1 controls Bak activation during TNFα induced cell death.

The proapoptotic protein Bak is implicated in the execution phase of apoptosis, a cell death program. Bak is essentially mitochondrial and during early steps of apoptosis undergoes conformational changes that lead to its full membrane integration in mitochondria and the subsequent liberation of pro-apoptotic mitochondrial proteins. Little is known about the partners and mechanisms implicated in...

Playing FullBAK

BAK is a pro-apoptotic BCL-2 protein that forms toxic mitochondrial pores in response to cellular stress. A membrane-embedded protein historically refractory to recombinant expression in full-length form, BAK plays it close to the vest. We recently produced monomeric, full-length BAK (FL-BAK) for the first time, 1 providing new opportunities to interrogate its activation mechanism as compared w...