MOMP in the absence of BH3-only proteins

Saez, Ana J Garcia; Villunger, Andreas

doi:10.1101/gad.281519.116

Cited by 8 publications

(4 citation statements)

References 13 publications

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“…However, this is contested by the reports, which show that when the BH3-only proteins are absent, BAK can still be activated by losing MCL-1 in nontransformed cells. 29 , 30 The second mechanism proposes that BH3-only proteins, competing against MCL-1, instead bind with BAK/BAX and the complexes formed by BH3-only proteins and BAK/BAX activate the apoptotic program. Based on the proposed mechanisms, the BH3-only proteins are also divided into two types, namely sensitizers and activators.…”

Section: Mcl-1 and Apoptosismentioning

confidence: 99%

MCL-1 inhibition in cancer treatment

Xiang

Yang

Bai

2018

OTT

117

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Myeloid cell leukemia-1 (MCL-1), a member of antiapoptotic BCL-2 family proteins, is a key regulator of mitochondrial homeostasis. Frequent overexpression of MCL-1 in human primary and drug-resistant cancer cells makes it an attractive cancer therapeutic target. Significant progress has been made in the development of small-molecule MCL-1 inhibitors in recent years, and three MCL-1 selective inhibitors have advanced to clinical trials. This review briefly discusses recent advances in the development of small molecules targeting MCL-1 for cancer therapy.

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Section: Mcl-1 and Apoptosismentioning

confidence: 99%

MCL-1 inhibition in cancer treatment

Xiang

Yang

Bai

2018

OTT

117

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“…Moreover, after successful phagocytosis of invading bacteria, neutrophils undergo apoptosis, a very important step for the resolution of inflammation, which is called phagocytosis-induced cell death (PICD). Exposure of the cell to an apoptotic stimulus frequently engages BH3-only proteins, either transcriptionally or translationally, which allows them to either directly (Bim and tBid) or indirectly (all BH3-only) activate the pro-apoptotic effector proteins Bax/Bak (Czabotar et al, 2014 ; Garcia Saez and Villunger, 2016 ).…”

Section: Neutrophils' Functions and Survivalmentioning

confidence: 99%

Manipulation of Neutrophils by Porphyromonas gingivalis in the Development of Periodontitis

Sochalska

Potempa

2017

Front. Cell. Infect. Microbiol.

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The pathogenesis of the chronic periodontal disease is associated with a skewed host inflammatory response to periodontal pathogens, such as Porphyromonas gingivalis, that accounts for the majority of periodontal tissue damage. Neutrophils are the most abundant leukocytes in periodontal pockets and depending on the stage of the disease, also plentiful PMNs are present in the inflamed gingival tissue and the gingival crevice. They are the most efficient phagocytes and eliminate pathogens by a variety of means, which are either oxygen-dependent or -independent. However, these secretory lethal weapons do not strictly discriminate between pathogens and host tissue. Current studies describe conflicting findings about neutrophil involvement in periodontal disease. On one hand literature indicate that hyper-reactive neutrophils are the main immune cell type responsible for this observed tissue damage and disease progression. Deregulation of neutrophil survival and functions, such as chemotaxis, migration, secretion of antimicrobial peptides or enzymes, and production of reactive oxygen species, contribute to observed tissue injury and the clinical signs of periodontal disease. On the other hand neutrophils deficiencies in patients and mice also result in periodontal phenotype. Therefore, P. gingivalis represents a periodontal pathogen that manipulates the immune responses of PMNs, employing several virulence factors, such as gingipains, serine proteases, lipid phosphatases, or fimbriae. This review will sum up studies devoted to understanding different strategies utilized by P. gingivalis to manipulate PMNs survival and functions in order to inhibit killing by a granular content, prolong inflammation, and gain access to nutrient resources.

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“…Apoptosis is essential for maintaining cellular homeostasis, and its aberrant regulation leads to a variety of disorders (12)(13)(14). Proapoptotic Bcl2 subfamily proteins are key proteins involved in the mitochondrial apoptotic pathway and can be further classified as either Bcl2 homology region 3 (BH3) domain-only members or multidomain Bcl2-associated X (Bax) and Bcl2 antagonist/killer (Bak) proteins (7).…”

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confidence: 99%

Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ‐related signaling pathway

Huang

Luo

et al. 2018

The FASEB Journal

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Methamphetamine (Meth) is a widely abused psychoactive drug that primarily damages the nervous system, notably causing dopaminergic neuronal apoptosis. CCAAT-enhancer binding protein (C/EBPβ) is a transcription factor and an important regulator of cell apoptosis and autophagy. Insulin-like growth factor binding protein (IGFBP5) is a proapoptotic factor that mediates Meth-induced neuronal apoptosis, and Trib3 (tribbles pseudokinase 3) is an endoplasmic reticulum (ER) stress-inducible gene involved in autophagic cell death through the mammalian target of rapamycin (mTOR) signaling pathway. To test the hypothesis that C/EBPβ is involved in Meth-induced IGFBP5-mediated neuronal apoptosis and Trib3-mediated neuronal autophagy, we measured the protein expression of C/EBPβ after Meth exposure and evaluated the effects of silencing C/EBPβ, IGFBP5, or Trib3 on Meth-induced apoptosis and autophagy in neuronal cells and in the rat striatum after intrastriatal Meth injection. We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity.-Xu, X., Huang, E., Luo, B., Cai, D., Zhao, X., Luo, Q., Jin, Y., Chen, L., Wang, Q., Liu, C., Lin, Z., Xie, W.-B., Wang, H. Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ-related signaling pathway.

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MOMP in the absence of BH3-only proteins

Cited by 8 publications

References 13 publications

MCL-1 inhibition in cancer treatment

MCL-1 inhibition in cancer treatment

Manipulation of Neutrophils by Porphyromonas gingivalis in the Development of Periodontitis

Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ‐related signaling pathway

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