Tumor cells deficient in the proapoptotic proteins Bak and Bax are resistant to chemotherapeutic drugs. Here, we demonstrate that murine embryonic fibroblasts deficient for both Bak and Bax are, however, efficiently killed by thapsigargin, a specific inhibitor of ER Ca(2+) pumps that induces ER stress by depleting ER Ca(2+) stores. In the presence of Bak and Bax, thapsigargin eliminates cells b...

Previous studies have shown that human immunodeficiency virus (HIV) protease cleaves procaspase 8 to a fragment, termed Casp8p41, that lacks caspase activity but nonetheless contributes to T cell apoptosis. Herein, we show that Casp8p41 contains a domain that interacts with the BH3-binding groove of pro-apoptotic Bak to cause Bak oligomerization, Bak-mediated membrane permeabilization, and cell...

Recently we reported that the BH3-only proteins Bim and Noxa bind tightly but transiently to the BH3-binding groove of Bak to initiate Bak homo-oligomerization. However, it is unclear how such tight binding can induce Bak homo-oligomerization. Here we report the ligand-induced Bak conformational changes observed in 3D models of Noxa·Bak and Bim·Bak refined by molecular dynamics simulations. In ...

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...

INTRODUCTION The molecular mechanism underlying mitochondrial BAK activation during apoptosis remains highly controversial. Two seemingly conflicting models have been proposed. In one, BAK requires so-called activating BH3 only proteins (aBH3) to initiate its conformation change. In the other, displacement from inhibitory pro-survival BCL-2 proteins (PBPs) and monomerization of BAK by PBP selec...

PURPOSE To characterize the effects of benzalkonium chloride (BAK) in THP-1 differentiated cells in vitro. METHODS Macrophages were obtained after differentiation of THP-1 cells, a human monocytic leukemia cell line. Macrophages were exposed for 24 h to 33 nM (10(-5)%) benzalkonium chloride (BAK), 10 nM dinitrochlorobenzene (DNCB), 100 ng/mL lipopolysaccharide (LPS), 5 ng/mL tumor necrosis fa...

OBJECTIVE To examine the efficacy, safety, and tolerability of travoprost 0.004% benzalkonium chloride (BAK)-free compared with previous use of latanoprost 0.005% in Japanese patients living in the US who had primary open-angle glaucoma or ocular hypertension. METHODS This was an open-label, multicenter, bilateral, intraindividual, and active-controlled study in which 20 Japanese American pat...

Said Bouhraoua ･Mohamed Ferioun ･Srhiouar Nassira ･Abdelali Boussakouran Akhazzane ･ Douae Belahcen ･Khalil Hammani ･Said Louahlia. J Plant Biotechnol 2023;50:115-26. https://doi.org/10.5010/JPB.2023.50.015.115

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...

The last few years have witnessed a renewed interest in “data-driven algorithm design” (Balcan 2020), the use of Machine Learning (ML) to tailor an distribution instances. More than decade ago, advances configuration (Hoos 2011) paved way for historical data modify algorithm’s (typically fixed, static) parameters. In discrete optimization (e.g., satisfiability, integer programming, etc.), exact...