ArticleThe Journal of biological chemistry2011
Sig1R protein regulates hERG channel expression through a post-translational mechanism in leukemic cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- Sigma-1 Receptor Specific Biological Functions, Protective Role, and Therapeutic Potential in Cardiovascular Diseases.Cardiovascular toxicology · 2025Review
- Integrins regulate hERG1 dynamics by girdin-dependent Gαi3: signaling and modeling in cancer cells.Life science alliance · 2024Article
- Article
- Integrated analysis of the voltage-gated potassium channel-associated gene KCNH2 across cancers.BMC bioinformatics · 2023Article
- Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.International journal of molecular sciences · 2023Review
- DNA topoisomerase 2-associated proteins PATL1 and PATL2 regulate the biogenesis of hERG KProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Sigma non-opioid receptor 1 is a potential therapeutic target for long QT syndrome.Nature cardiovascular research · 2022Article
- Potassium and Calcium Channel Complexes as Novel Targets for Cancer Research.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders.Neuroscience and biobehavioral reviews · 2022Review
- Sigma-1 Receptor (S1R) Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases.International journal of molecular sciences · 2021Article
- Sigma-1 receptor ligands improves ventricular repolarization-related ion remodeling in rats with major depression disorder.Psychopharmacology · 2021Article
- Sigmar1's Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology.Frontiers in physiology · 2021Review
- Molecular Choreography and Structure of CaMembranes · 2020Review
- Polymer-Based Functional Cantilevers Integrated with Interdigitated Electrode Arrays-A Novel Platform for Cardiac Sensing.Micromachines · 2020Article
- Is the sigma-1 receptor a potential pharmacological target for cardiac pathologies? A systematic review.International journal of cardiology. Heart & vasculature · 2020Review
- The Molecular Function of σ Receptors: Past, Present, and Future.Trends in pharmacological sciences · 2019Review
- Molecular Interplay Between the Sigma-1 Receptor, Steroids, and Ion Channels.Frontiers in pharmacology · 2019Review
- Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases.Frontiers in neuroscience · 2019Review
- Small-Molecule Modulators of Sigma1 and Sigma2/TMEM97 in the Context of Cancer: Foundational Concepts and Emerging Themes.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sig1R (Sigma-1receptor) is a 25-kDa protein structurally unrelated to other mammalian proteins. Sig1R is present in brain, liver, and heart and is overexpressed in cancer cells. Studies using exogenous sigma ligands have shown that Sig1R interacts with a variety of ion channels, but its intrinsic function and mechanism of action remain unclear. The human ether-à-gogo related gene (hERG) encodes a cardiac channel that is also abnormally expressed in many primary human cancers, potentiating tumor progression through the modulation of extracellular matrix adhesive interactions. We show herein that sigma ligands inhibit hERG current density and cell adhesion to fibronectin in K562 myeloid leukemia cells. Heterologous expression in Xenopus oocytes demonstrates that Sig1R potentiates hERG current by stimulating channel subunit biosynthesis. Silencing Sig1R in leukemic K562 cells depresses hERG current density and cell adhesion to fibronectin by reducing hERG membrane expression. In K562 cells, Sig1R silencing does not modify hERG mRNA contents but reduces hERG mature form densities. In HEK cells expressing hERG and Sig1R, both proteins co-immunoprecipitate, demonstrating a physical association. Finally, Sig1R expression enhances both channel protein maturation and stability. Altogether, these results demonstrate for the first time that Sig1R controls ion channel expression through the regulation of subunit trafficking activity.
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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.