Trial reportBlood2012
Integrated protein quality-control pathways regulate free α-globin in murine β-thalassemia.
Trial report in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 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.
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
67 citing papers in PubMed, 99 citations in OpenAlex.
- New Gene Therapy Strategy for β-Thalassemia.Stem cell reviews and reports · 2026Review
- Red blood cell membrane proteome as a reporter of disease severity, transfusion impact and genetic background in transfusion-dependent β-thalassaemia.British journal of haematology · 2026Article
- Multiomics analysis of red blood cells reveals thalassemia severity beyond globin gene mutations.Blood advances · 2026Article
- Article
- Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.MedComm · 2026Review
- Single-Position Peptide Clustering for Peptidomics Reveals Novel Disease Biomarkers and Dysregulated Proteolytic Characteristics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular and biochemical heterogeneity contributes to the phenotypic diversity of transfusion-dependent β-thalassemia.Blood advances · 2025Article
- Rapid detection of genetic modifiers of β-thalassemia based on MALDI-TOF MS.Annals of hematology · 2025Article
- Co-Induction of ULK-1 and AHSP mRNAs in Erythroid Precursor Cells Isolated From a Sirolimus-Treated β-Thalassemia Patient: A Case Report Study.British journal of biomedical science · 2025Article
- Mitoxantrone ameliorates ineffective erythropoiesis in a β-thalassemia intermedia mouse model.Blood advances · 2024Article
- Proteasome gene expression is controlled by coordinated functions of multiple transcription factors.The Journal of cell biology · 2024Article
- Mitochondrial regulation of erythropoiesis in homeostasis and disease.British journal of haematology · 2024Review
- Review
- Interplay between α-thalassemia and β-hemoglobinopathies: Translating genotype-phenotype relationships into therapies.HemaSphere · 2024Article
- Autologous gene therapy for hemoglobinopathies: From bench to patient's bedside.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Increased Expression of α-Hemoglobin Stabilizing Protein (AHSP) mRNA in Erythroid Precursor Cells Isolated from β-Thalassemia Patients Treated with Sirolimus (Rapamycin).Journal of clinical medicine · 2024Article
- Impact of α-Globin Gene Expression and α-Globin Modifiers on the Phenotype of β-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management.International journal of molecular sciences · 2024Review
- Decrease in α-Globin and Increase in the Autophagy-Activating Kinase ULK1 mRNA in Erythroid Precursors from β-Thalassemia Patients Treated with Sirolimus.International journal of molecular sciences · 2023Article
- Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype.Nature communications · 2023Article
- Novel potential therapeutics to modify iron metabolism and red cell synthesis in diseases associated with defective erythropoiesis.Haematologica · 2023Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cells remove unstable polypeptides through protein quality-control (PQC) pathways such as ubiquitin-mediated proteolysis and autophagy. In the present study, we investigated how these pathways are used in β-thalassemia, a common hemoglobinopathy in which β-globin gene mutations cause the accumulation and precipitation of cytotoxic α-globin subunits. In β-thalassemic erythrocyte precursors, free α-globin was polyubiquitinated and degraded by the proteasome. These cells exhibited enhanced proteasome activity, and transcriptional profiling revealed coordinated induction of most proteasome subunits that was mediated by the stress-response transcription factor Nrf1. In isolated thalassemic cells, short-term proteasome inhibition blocked the degradation of free α-globin. In contrast, prolonged in vivo treatment of β-thalassemic mice with the proteasome inhibitor bortezomib did not enhance the accumulation of free α-globin. Rather, systemic proteasome inhibition activated compensatory proteotoxic stress-response mechanisms, including autophagy, which cooperated with ubiquitin-mediated proteolysis to degrade free α-globin in erythroid cells. Our findings show that multiple interregulated PQC responses degrade excess α-globin. Therefore, β-thalassemia fits into the broader framework of protein-aggregation disorders that use PQC pathways as cell-protective mechanisms.
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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.