ArticleThe Journal of biological chemistry2015
Cellular FLICE-like Inhibitory Protein (c-FLIP) and PS1-associated Protein (PSAP) Mediate Presenilin 1-induced γ-Secretase-dependent and -independent Apoptosis, Respectively.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Megalin: from structure to function.Nature reviews. Nephrology · 2026Review
- Mitochondrial Dynamics and SLC25 Transporters in Neurodegeneration: From Mechanisms to Therapeutic Opportunities.Biomolecules · 2026Review
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Increased expression of the proapoptotic presenilin associated protein is involved in neuronal tangle formation in human brain.Scientific reports · 2024Article
- Dysfunction of Drosophila mitochondrial carrier homolog (Mtch) alters apoptosis and disturbs development.FEBS open bio · 2024Article
- Mitochondrial carrier 1 (MTCH1) governs ferroptosis by triggering the FoxO1-GPX4 axis-mediated retrograde signaling in cervical cancer cells.Cell death & disease · 2023Article
- Potential of Therapeutic Small Molecules in Apoptosis Regulation in the Treatment of Neurodegenerative Diseases: An Updated Review.Molecules (Basel, Switzerland) · 2022Review
- Susceptibility to cellular stress in PS1 mutant N2a cells is associated with mitochondrial defects and altered calcium homeostasis.Scientific reports · 2020Article
- Soluble epoxide hydrolase promotes astrocyte survival in retinopathy of prematurity.The Journal of clinical investigation · 2019Article
- New Lipid Mediators in Retinal Angiogenesis and Retinopathy.Frontiers in pharmacology · 2019Review
- Inhibition of the Neuronal Calcium Sensor DREAM Modulates Presenilin-2 Endoproteolysis.Frontiers in molecular neuroscience · 2018Article
- Article
- Familial Alzheimer's Disease Lymphocytes Respond Differently Than Sporadic Cells to Oxidative Stress: Upregulated p53-p21 Signaling Linked with Presenilin 1 Mutants.Molecular neurobiology · 2017Article
- Nicastrin is required for amyloid precursor protein (APP) but not Notch processing, while anterior pharynx-defective 1 is dispensable for processing of both APP and Notch.Journal of neurochemistry · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Presenilin 1 (PS1) has been implicated in apoptosis; however, its mechanism remains elusive. We report that PS1-induced apoptosis was associated with cellular FLICE-like inhibitory protein (c-FLIP) turnover and that γ-secretase inhibitor blocked c-FLIP turnover and also partially blocked PS1-induced apoptosis. A complete inhibition of PS1-induced apoptosis was achieved by knockdown of PS1-associated protein (PSAP), a mitochondrial proapoptotic protein that forms a complex with Bax upon induction of apoptosis, in the presence of γ-secretase inhibitor. PS1-induced apoptosis was partially inhibited by knockdown of caspase-8, Fas-associated protein with death domain (FADD), or Bid. However, knockdown of Bax or overexpression of Bcl-2 resulted in complete inhibition of PS1-induced apoptosis. These data suggest that PS1 induces apoptosis through two pathways: the γ-secretase-dependent pathway mediated by turnover of c-FLIP and the γ-secretase-independent pathway mediated by PSAP-Bax complex formation. These two pathways converge on Bax to activate mitochondria-dependent apoptosis. These findings provide new insight into the mechanisms by which PS1 is involved in apoptosis and the mechanism by which PS1 exerts its pathogenic effects. In addition, our results suggest that PS2 induces apoptosis through a pathway that is different from that of PS1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.