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Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics.
TLDR
A two-class model for BH3 domains is supported: BID-like domains that "activate" BAX, BAK and BAD-like domain that "sensitize" by occupying the pocket of antiapoptotic members.
JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy.
TLDR
It is demonstrated that JNK1-mediated multisite phosphorylation of Bcl-2 stimulates starvation-induced autophagy by disrupting the B cl-2/Beclin 1 complex, which defines a mechanism that cells use to regulate autophagic activity in response to nutrient status.
Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation
TLDR
This work identifies rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%-99% knockdown with minimal off-target effects, and activators to endogenous genes via endonuclease-deficient Cas9, which enable modulation of gene expression over a ∼1,000-fold range.
Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis
TLDR
It is shown that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice and BCL2 is a crucial regulator of exercise- (and starvation)-induced autophagic induction in vivo, which may contribute to the beneficial metabolic effects of exercise.
Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum.
TLDR
The findings support a model in which BCL-2 family members regulate IP3R-1 phosphorylation to control the rate of ER Ca(2+) leak from intracellular stores.
Proapoptotic BAX and BAK Modulate the Unfolded Protein Response by a Direct Interaction with IRE1α
TLDR
BAX and BAK function at the ER membrane to activate IRE1α signaling and to provide a physical link between members of the core apoptotic pathway and the UPR.
A Systematic Mammalian Genetic Interaction Map Reveals Pathways Underlying Ricin Susceptibility
TLDR
The ability to rapidly generate mammalian GI maps provides a potentially transformative tool for defining gene function and designing combination therapies based on synergistic pairs.
Phosphorylation of BCL‐2 regulates ER Ca2+ homeostasis and apoptosis
TLDR
[Ca2+]er proved coordinate with the capacity of BCL‐2 to bind proapoptotic BH3‐only members, further integrating the apoptotic pathway and Ca2+ modulation.
CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity
TLDR
Insight is provided into the biology of PD-L1 regulation, a previously unrecognized master regulator of this critical immune checkpoint is identified, and a potential therapeutic target to overcome immune evasion by tumour cells is highlighted.
Biochemical and Genetic Analysis of the Mitochondrial Response of Yeast to BAX and BCL-XL
TLDR
It is found that in wild-type yeast, BAX induced hyperpolarization of mitochondria, production of reactive oxygen species, growth arrest, and cell death; however, cytochrome c was not released detectably despite the induction of mitochondrial dysfunction.
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