ArticleCell death and differentiation2013
Identification of PTEN at the ER and MAMs and its regulation of Ca(2+) signaling and apoptosis in a protein phosphatase-dependent manner.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
134 citing papers in PubMed, 229 citations in OpenAlex.
- Mitochondria as the Hub of Apoptosis: A Comprehensive Insight From Mitochondria to Interactions With Other Organelles.MedComm · 2026Review
- MANF safeguards mitochondria-associated endoplasmic reticulum membrane integrity in nucleus pulposus-derived mesenchymal stem cells to maintain homeostasis of the intervertebral disc.Cell biology and toxicology · 2026Article
- Calcium and TRPML-Mediated Autophagy: Implications in Cancer, Cardiovascular Diseases, and Cardio-Oncology.Cardiovascular toxicology · 2026Review
- PTEN Subcellular Localization Dictates Function.bioRxiv : the preprint server for biology · 2026Article
- Organelle contact sites in cancer cells.Cell death & disease · 2026Review
- Mitochondria-ER crosstalk via MAMS: Bridging cellular homeostasis and cancer progression.Apoptosis : an international journal on programmed cell death · 2026Review
- The Role of Mitochondrial ROS in Neoplastic Transformations, Progression and Therapeutic Targeting.Oncology research · 2026Review
- The role of mitochondrial-associated endoplasmic reticulum membranes (MAMs) in diabetic microvascular complications: a review.Cell death & disease · 2025Review
- Beyond tumour suppression: cGAS-STING pathway in urologic malignancies: Context-dependent duality and therapeutic implications.Clinical and translational medicine · 2025Review
- The Role of Mitochondria-Associated Endoplasmic Reticulum Membranes in Fibrotic Diseases.Aging and disease · 2025Review
- Expression of Apoptosis-Associated Proteins in Tumor Cells under Autophagy and Endoplasmic Reticulum Stress Stimulation in Mouse Skin Melanoma Model.Bulletin of experimental biology and medicine · 2025Article
- The impact of ERCell death & disease · 2025Article
- Bypassing the guardian: regulated cell death pathways in p53-mutant cancers.Cellular & molecular biology letters · 2025Review
- The perspective of modern transplant science - transplant arteriosclerosis: inspiration derived from mitochondria associated endoplasmic reticulum membrane dysfunction in arterial diseases.International journal of surgery (London, England) · 2025Review
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Modification in Structures of Active Compounds in Anticancer Mitochondria-Targeted Therapy.International journal of molecular sciences · 2025Review
- The correlation between mitochondria-associated endoplasmic reticulum membranes (MAMs) and CaActa pharmacologica Sinica · 2025Review
- Exploring Negative Feedback Mechanisms in the PTEN-ACE Axis: Application of Electrosorb Hydrogel-Based Gene Delivery for Intervertebral Disc Regeneration.International journal of biological sciences · 2025Article
- Endoplasmic reticulum-mitochondria crosstalk: new mechanisms in the development of atherosclerosis.Frontiers in endocrinology · 2025Review
- The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The tumor suppressor activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10) is thought to be largely attributable to its lipid phosphatase activity. PTEN dephosphorylates the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate to directly antagonize the phosphoinositide 3-kinase-Akt pathway and prevent the activating phosphorylation of Akt. PTEN has also other proposed mechanisms of action, including a poorly characterized protein phosphatase activity, protein-protein interactions, as well as emerging functions in different compartment of the cells such as nucleus and mitochondria. We show here that a fraction of PTEN protein localizes to the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs), signaling domains involved in calcium ((2+)) transfer from the ER to mitochondria and apoptosis induction. We demonstrate that PTEN silencing impairs ER Ca(2+) release, lowers cytosolic and mitochondrial Ca(2+) transients and decreases cellular sensitivity to Ca(2+)-mediated apoptotic stimulation. Specific targeting of PTEN to the ER is sufficient to enhance ER-to-mitochondria Ca(2+) transfer and sensitivity to apoptosis. PTEN localization at the ER is further increased during Ca(2+)-dependent apoptosis induction. Importantly, PTEN interacts with the inositol 1,4,5-trisphosphate receptors (IP3Rs) and this correlates with the reduction in their phosphorylation and increased Ca(2+) release. We propose that ER-localized PTEN regulates Ca(2+) release from the ER in a protein phosphatase-dependent manner that counteracts Akt-mediated reduction in Ca(2+) release via IP3Rs. These findings provide new insights into the mechanisms and the extent of PTEN tumor-suppressive functions, highlighting new potential strategies for therapeutic intervention.
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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.