ArticleThe Journal of cell biology2012
MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound β(2)-adrenergic receptors.
Article in The Journal of cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Review
- The role of ubiquitin system in ageing-related diseases and potential therapeutic opportunities.Molecular biomedicine · 2026Review
- MARCH2 prevents doxorubicin-induced cardiomyopathy by stabilizing NR1H2 and promoting clearance of apoptotic cardiomyocytes.Nature communications · 2026Article
- MARCH2-mediated Lys63-linked polyubiquitination promotes metastasis by modulating the catalytic activity of TGF-β type I receptor.Cell death & disease · 2025Article
- βmedRxiv : the preprint server for health sciences · 2025Article
- The E3 ubiquitin ligase MARCH2 controls TNF-α mediated inflammation by autoubiquitination.Cell communication and signaling : CCS · 2025Article
- Role of MARCH E3 ubiquitin ligases in cancer development.Cancer metastasis reviews · 2024Review
- MARCH2, a T cell specific factor that restricts HIV-1 infection.PLoS pathogens · 2024Article
- MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases.Cancer research communications · 2024Article
- β-adrenergic receptor signaling mediated by β-arrestins and its potential role in heart failure.Current opinion in physiology · 2024Article
- Unique Positive Cooperativity Between theMolecular pharmacology · 2021Article
- Development of a Novel SNAP-Epitope Tag/Near-Infrared Imaging Assay to Quantify G Protein-Coupled Receptor Degradation in Human Cells.SLAS discovery : advancing life sciences R & D · 2021Article
- Post-Translational Modifications of G Protein-Coupled Receptors Control Cellular Signaling Dynamics in Space and Time.Pharmacological reviews · 2021Review
- Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling.The Journal of biological chemistry · 2020Article
- Negative regulation of NEMO signaling by the ubiquitin E3 ligase MARCH2.The EMBO journal · 2020Article
- The E3 ubiquitin ligase MARCH2 regulates ERGIC3-dependent trafficking of secretory proteins.The Journal of biological chemistry · 2019Article
- A serine in the first transmembrane domain of the human E3 ubiquitin ligase MARCH9 is critical for down-regulation of its protein substrates.The Journal of biological chemistry · 2019Article
- The deubiquitinase ubiquitin-specific protease 20 is a positive modulator of myocardial βThe Journal of biological chemistry · 2019Article
- GPCR desensitization: Acute and prolonged phases.Cellular signalling · 2018Review
- Mdm2 regulates cardiac contractility by inhibiting GRK2-mediated desensitization of β-adrenergic receptor signaling.JCI insight · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Lysosomal degradation of ubiquitinated β(2)-adrenergic receptors (β(2)ARs) serves as a major mechanism of long-term desensitization in response to prolonged agonist stimulation. Surprisingly, the βAR antagonist carvedilol also induced ubiquitination and lysosomal trafficking of both endogenously expressed β(2)ARs in vascular smooth muscle cells (VSMCs) and overexpressed Flag-β(2)ARs in HEK-293 cells. Carvedilol prevented β(2)AR recycling, blocked recruitment of Nedd4 E3 ligase, and promoted the dissociation of the deubiquitinases USP20 and USP33. Using proteomics approaches (liquid chromatography-tandem mass spectrometry), we identified that the E3 ligase MARCH2 interacted with carvedilol-bound β(2)AR. The association of MARCH2 with internalized β(2)ARs was stabilized by carvedilol and did not involve β-arrestin. Small interfering RNA-mediated down-regulation of MARCH2 ablated carvedilol-induced ubiquitination, endocytosis, and degradation of endogenous β(2)ARs in VSMCs. These findings strongly suggest that specific ligands recruit distinct E3 ligase machineries to activated cell surface receptors and direct their intracellular itinerary. In response to β blocker therapy with carvedilol, MARCH2 E3 ligase activity regulates cell surface β(2)AR expression and, consequently, its signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.