ArticleThe Journal of biological chemistry2012
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein-induced lysosomal translocation of proapoptotic effectors is mediated by phosphofurin acidic cluster sorting protein-2 (PACS-2).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Pooled it
- PACS2 at Mitochondria-Associated Membranes: A Central Regulator of Cardiovascular and Metabolic Diseases.Journal of cellular and molecular medicine · 2026Review
- Macrophage FTO deficiency accelerates atherosclerosis via PACS2-mediated activation of the PPARγ lipid signaling pathway.Journal of translational medicine · 2026Article
- Understanding PACS2 syndrome's pathomechanism by studying E209K and E211K mutations.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- DR5 is a restriction factor for human herpesviruses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PACS-2 deficiency aggravates tubular injury in diabetic kidney disease by inhibiting ER-phagy.Cell death & disease · 2023Article
- Mitochondria-associated membrane protein PACS2 maintains right cardiac function in hypobaric hypoxia.iScience · 2023Article
- Therapeutic targeting of TRAIL death receptors.Biochemical Society transactions · 2023Review
- The Phosphofurin Acidic Cluster Sorting Protein 2 (PACS-2) E209K Mutation Responsible for PACS-2 Syndrome Increases Susceptibility to Apoptosis.ACS omega · 2022Article
- PACS-2 attenuates diabetic kidney disease via the enhancement of mitochondria-associated endoplasmic reticulum membrane formation.Cell death & disease · 2021Article
- Molecular Dysfunctions of Mitochondria-Associated Endoplasmic Reticulum Contacts in Atherosclerosis.Oxidative medicine and cellular longevity · 2021Review
- Molecular Dysfunctions of Mitochondria-Associated Membranes (MAMs) in Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Filamin B extensively regulates transcription and alternative splicing, and is associated with apoptosis in HeLa cells.Oncology reports · 2020Article
- Isosteviol Protects Free Fatty Acid- and High Fat Diet-Induced Hepatic InjuryAntioxidants & redox signaling · 2019Article
- Developing TRAIL/TRAIL death receptor-based cancer therapies.Cancer metastasis reviews · 2018Review
- A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar Dysgenesis.American journal of human genetics · 2018Article
- Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.Cell death and differentiation · 2018Review
- Caught in the act - protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease.Journal of cell science · 2017Review
- Aberrant DR5 transport through disruption of lysosomal function suggests a novel mechanism for receptor activation.Oncotarget · 2016Article
- PACS-2 mediates the ATM and NF-κB-dependent induction of anti-apoptotic Bcl-xL in response to DNA damage.Cell death and differentiation · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of liver cancer cell lines requires death receptor-5 (DR5)-dependent permeabilization of lysosomal membranes. Ligated DR5 triggers recruitment of the proapoptotic proteins Bim and Bax to lysosomes, releasing cathepsin B into the cytosol where it mediates mitochondria membrane permeabilization and activation of executioner caspases. Despite the requirement for lysosome membrane permeabilization during TRAIL-induced apoptosis, little is known about the mechanism that controls recruitment of Bim and Bax to lysosomal membranes. Here we report that TRAIL induces recruitment of the multifunctional sorting protein phosphofurin acidic cluster sorting protein-2 (PACS-2) to DR5-positive endosomes in Huh-7 cells where it forms an immunoprecipitatable complex with Bim and Bax on lysosomal membranes. shRNA-targeted knockdown of PACS-2 prevents recruitment of Bim or Bax to lysosomes, blunting the TRAIL-induced lysosome membrane permeabilization. Consistent with the reduced lysosome membrane permeabilization, shRNA knockdown of PACS-2 in Huh-7 cells reduced TRAIL-induced apoptosis and increased clonogenic cell survival. The determination that recombinant PACS-2 bound Bim but not Bax in vitro and that shRNA knockdown of Bim blocked Bax recruitment to lysosomes suggests that TRAIL/DR5 triggers endosomal PACS-2 to recruit Bim and Bax to lysosomes to release cathepsin B and induce apoptosis. Together, these findings provide insight into the lysosomal pathway of apoptosis.
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Registered trials
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.