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The BCL-2 protein family: opposing activities that mediate cell death

TLDR
New insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, but a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.
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Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy

TLDR
The biochemical, structural and genetic studies that have clarified how the interplay between members of the BCL-2 family on mitochondria sets the apoptotic threshold are discussed, illuminating the physiological control of apoptosis, the pathological consequences of its dysregulation and the promising search for novel cancer therapies that target the BCA2 protein family.
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Apoptosis Initiated When BH3 Ligands Engage Multiple Bcl-2 Homologs, Not Bax or Bak

TLDR
Contrary to the direct-activation model, it is shown that Bax and Bak can mediate apoptosis without discernable association with the putative BH3-only activators (Bim, Bid, and Puma).
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Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

TLDR
An updated classification of cell death subroutines focusing on mechanistic and essential aspects of the process is proposed, and the utility of neologisms that refer to highly specialized instances of these processes are discussed.
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ER Stress Triggers Apoptosis by Activating BH3-Only Protein Bim

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Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity.

TLDR
Gene targeting in mice revealed important physiological roles for Bim and revealed that Bim is required for hematopoietic homeostasis and as a barrier to autoimmunity.
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Bim: a novel member of the Bcl‐2 family that promotes apoptosis

TLDR
Bim appears to act as a ‘death ligand’ which can only neutralize certain members of the pro‐survival Bcl‐2 sub‐family.
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p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa

TLDR
In mice with either noxa or puma disrupted, decreased DNA damage–induced apoptosis in fibroblasts is observed, although only loss of Puma protected lymphocytes from cell death, and Puma deficiency protected cells against diverse p53-independent cytotoxic insults.
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The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex.

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Apoptosis signaling.

TLDR
Current knowledge of apoptosis signaling is reviewed, several pressing questions are listed, and a novel model is presented to explain the biochemical and functional interactions between components of the cell death regulatory machinery.
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