Apaf-1: Regulation and function in cell death

Shakeri, Raheleh; Kheirollahi, Asma; Davoodi, Jamshid

doi:10.1016/j.biochi.2017.02.001

Cited by 254 publications

(176 citation statements)

References 186 publications

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“…Apoptosome formation is among the best‐characterized mechanisms mediating activation of initiator caspases. A clear delineation of the sequential events required for apoptosome formation have been described . At the initiation stages of apoptosis, mitochondrial cytochrome c is released into the cytosol.…”

Section: Aim2 Activation Leads To Inflammasome Assemlymentioning

confidence: 99%

“…A clear delineation of the sequential events required for apoptosome formation have been described. 30 At the initiation stages of apoptosis, mitochondrial cytochrome c is released into the cytosol. Then, cytochrome c binds apoptotic protease activating factor-1 (Apaf-1), triggering a conformational change that results in its oligomerization and recruitment of caspase-9.…”

Section: Inflammasomes Are Caspase-activating Machinesmentioning

confidence: 99%

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The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

Lugrin

Martinon

2017

Immunological Reviews

290

205

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Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. However, AIM2 achieves specificity by detecting altered or mislocalized DNA molecules. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment such as genomic DNA released into the cytosol upon loss of nuclear envelope integrity. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. This triggers the maturation and secretion of the cytokines IL-1β and IL-18. It can also initiate pyroptosis, a proinflammatory form of cell death. The AIM2 inflammasome contributes to physiological responses and diseases. It is a key player in host defenses, but its deregulation can contribute immune-linked diseases, such as autoinflammatory and autoimmune pathologies. Moreover, AIM2 may play a role in cancer development. Recent studies have shown that the detection of self-DNA species by AIM2 is an important factor that contributes to diseases associated with perturbation of cellular homeostasis. Thus, in addition of being a sensor of pathogen associated molecular patterns (PAMPs), the AIM2 inflammasome is emerging as a key guardian of cellular integrity.

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Section: Aim2 Activation Leads To Inflammasome Assemlymentioning

confidence: 99%

Section: Inflammasomes Are Caspase-activating Machinesmentioning

confidence: 99%

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

Lugrin

Martinon

2017

Immunological Reviews

290

205

View full text Add to dashboard Cite

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“…This recruitment occurs through the exposure of the caspase activation and recruitment domains (CARD) in Apaf‐1 . Through caspase‐9 dimerization, the apoptosome is activated, which then cleaves and activates, caspase‐3 and caspase‐7 , causing severe cell death (Figure ) .…”

Section: Mitochondrion‐related Cytotoxicitymentioning

confidence: 99%

Mitochondrial integrity in neurodegeneration

2019

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Summary The mitochondrion is a unique organelle with a diverse range of functions. Mitochondrial dysfunction is a key pathological process in several neurodegenerative diseases. Mitochondria are mostly important for energy production; however, they also have roles in Ca 2+ homeostasis, ROS production, and apoptosis. There are two major systems in place, which regulate mitochondrial integrity, mitochondrial dynamics, and mitophagy. These two processes remove damaged mitochondria from cells and protect the functional mitochondrial population. These quality control systems often become dysfunctional during neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, causing mitochondrial dysfunction and severe neurological symptoms.

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“…A notable difference, however, is the apparent absence of the SAMD9 family proteins in plants. The architectural similarity between SAMD9 and STAND complements the sequence similarity between the NTPase domain of SAMD9 and the nucleotide-binding and oligomerization domain (NOD) of Apaf1, the major component of the animal apoptosome, the key mediator of programmed cell death [24, 25]. Another strong connection to apoptosis and inflammation is the presence, in fish and invertebrate members of the SAMD9 family, of CARD, Death, PYRIN and FIIND domains (Fig.…”

Section: Resultsmentioning

confidence: 99%

The complex domain architecture of SAMD9 family proteins, predicted STAND-like NTPases, suggests new links to inflammation and apoptosis

2017

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We report a comprehensive computational dissection of the domain architecture of the SAMD9 family proteins that are involved in antivirus and antitumor response in humans. We show that the SAMD9 protein family is represented in most animals and also, unexpectedly, in bacteria, in particular actinomycetes. From the N to C terminus, the core SAMD9 family architecture includes DNA/RNA-binding AlbA domain, a variant Sir2-like domain, a STAND-like P-loop NTPase, an array of TPR repeats and an OB-fold domain with predicted RNA-binding properties. Vertebrate SAMD9 family proteins contain the eponymous SAM domain capable of polymerization, whereas some family members from other animals instead contain homotypic adaptor domains of the DEATH superfamily, known as dedicated components of apoptosis networks. Such complex domain architecture is reminiscent of the STAND superfamily NTPases that are involved in various signaling processes, including programmed cell death, in both eukaryotes and prokaryotes. These findings suggest that SAMD9 is a hub of a novel, evolutionarily conserved defense network that remains to be characterized.ReviewersThis article was reviewed by Igor B. Zhulin and Mensur Dlakic.Electronic supplementary materialThe online version of this article (doi:10.1186/s13062-017-0185-2) contains supplementary material, which is available to authorized users.

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Apaf-1: Regulation and function in cell death

Cited by 254 publications

References 186 publications

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

Mitochondrial integrity in neurodegeneration

The complex domain architecture of SAMD9 family proteins, predicted STAND-like NTPases, suggests new links to inflammation and apoptosis

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