ArticleBlood2013
Eukaryotic initiation factor 2α phosphorylation mediates fetal hemoglobin induction through a post-transcriptional mechanism.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease.Expert review of hematology · 2015Pooled it
- The dual role of ATF3 in myocardial repair through macrophage regulation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 2025Review
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- Allogeneic hematopoietic stem cell transplantation to cure sickle cell disease: A review.Frontiers in medicine · 2023Review
- PUM1 mediates the posttranscriptional regulation of human fetal hemoglobin.Blood advances · 2022Article
- Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- RGS5 Determines Neutrophil Migration in the Acute Inflammatory Phase of Bleomycin-Induced Lung Injury.International journal of molecular sciences · 2021Article
- Article
- Pathophysiology and recent therapeutic insights of sickle cell disease.Annals of hematology · 2020Review
- Global translational repression induced by iron deficiency in yeast depends on the Gcn2/eIF2α pathway.Scientific reports · 2020Article
- TFII-I/Gtf2i and Erythro-Megakaryopoiesis.Frontiers in physiology · 2020Article
- Review
- Highly efficient editing of the β-globin gene in patient-derived hematopoietic stem and progenitor cells to treat sickle cell disease.Nucleic acids research · 2019Article
- Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells.Science (New York, N.Y.) · 2018Article
- Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells.Blood · 2018Article
- The eIF2-alpha kinase HRI: a potential target beyond the red blood cell.Expert opinion on therapeutic targets · 2017Review
- UIS2: A Unique Phosphatase Required for the Development of Plasmodium Liver Stages.PLoS pathogens · 2016Article
- Stress-enhanced translation of γ-globin mRNA.Blood · 2014Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Strategies to increase fetal hemoglobin (HbF) levels can ameliorate symptoms and improve the lives of β-hemoglobinopathy patients. Although most studies have focused on induction of γ-globin gene expression as an approach to induce HbF, we hypothesized that post-transcriptional regulation of HbF plays an underappreciated yet important role in controlling HbF levels. In the present study, we investigated whether increasing eukaryotic initiation factor 2α (eIF2α) phosphorylation, a key regulator of protein translation, could enhance HbF post-transcriptionally in human primary erythroid cells. Initial analysis using a known inhibitor of eIF2α dephosphorylation, salubrinal, revealed that elevated eIF2α phosphorylation enhanced HbF production without changing globin gene expression, proliferation, or cell differentiation. These results were further supported by the post-transcriptional induction of HbF by other pharmacologic activators of the eIF2α pathway and by genetic inactivation of the negative regulators, GADD34 and CReP. Additionally, we found that this novel mechanism of increasing HbF could be combined with clinically relevant transcriptional activators of γ-globin gene expression to additively enhance HbF. Taken together, these findings identify eIF2α phosphorylation as a post-transcriptional regulator of HbF induction that may be pharmacologically targeted, either alone or in combination, in β-hemoglobinopathy patients.
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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.