ArticleExperimental hematology2008
E3 ligase FLRF (Rnf41) regulates differentiation of hematopoietic progenitors by governing steady-state levels of cytokine and retinoic acid receptors.
Article in Experimental hematology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- E3 ubiquitin ligase on the biological properties of hematopoietic stem cell.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Article
- The ubiquitin ligase HECTD1 promotes retinoic acid signaling required for development of the aortic arch.Disease models & mechanisms · 2019Article
- CACYBP Enhances Cytoplasmic Retention of P27Theranostics · 2019Article
- Erythropoietin Receptor Signaling and Lipid Rafts.Vitamins and hormones · 2017Review
- Article
- Ubiquitin-specific Protease-7 Inhibition Impairs Tip60-dependent Foxp3+ T-regulatory Cell Function and Promotes Antitumor Immunity.EBioMedicine · 2016Article
- The ER structural protein Rtn4A stabilizes and enhances signaling through the receptor tyrosine kinase ErbB3.Science signaling · 2016Article
- Lenalidomide Stabilizes the Erythropoietin Receptor by Inhibiting the E3 Ubiquitin Ligase RNF41.Cancer research · 2016Article
- Ubiquitylation of nuclear receptors: new linkages and therapeutic implications.Journal of molecular endocrinology · 2015Review
- Regulation of ERBB3/HER3 signaling in cancer.Oncotarget · 2014Review
- Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets.Scientific reports · 2014Article
- Oligomerization of the Nrdp1 E3 ubiquitin ligase is necessary for efficient autoubiquitination but not ErbB3 ubiquitination.The Journal of biological chemistry · 2014Article
- Phosphorylation of the E3 ubiquitin ligase RNF41 by the kinase Par-1b is required for epithelial cell polarity.Journal of cell science · 2014Article
- Regulation of IL-4 receptor signaling by STUB1 in lung inflammation.American journal of respiratory and critical care medicine · 2014Article
- Genetic screen for regulators of lymph gland homeostasis and hemocyte maturation in Drosophila.G3 (Bethesda, Md.) · 2012Article
- RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding.Journal of cell science · 2011Article
- Molecular mechanisms of leukemia-associated protein degradation.Frontiers of medicine in China · 2010Review
- Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL).PloS one · 2009Article
- T-cell differentiation of multipotent hematopoietic cell line EML in the OP9-DL1 coculture system.Experimental hematology · 2009Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveFLRF (Rnf41) gene was identified through screening of subtracted cDNA libraries form murine hematopoietic stem cells and progenitors. Subsequent work has revealed that FLRF acts as E3 ubiquitin ligase, and that it regulates steady-state levels of neuregulin receptor ErbB3 and participates in degradation of IAP protein BRUCE and parkin. The objective of this study was to start exploring the role of FLRF during hematopoiesis. MATERIALS AND
methodsFLRF was overexpressed in a murine multipotent hematopoietic progenitor cell line EML, which can differentiate into almost all blood cell lineages, and in pro-B progenitor cell line BaF3. The impact of FLRF overexpression on EML cell differentiation into myeloerythroid lineages was studied using hematopoietic colony-forming assays. The interaction of FLRF with cytokine receptors and receptor levels in control cells and EML and BaF3 cells overexpressing FLRF were examined with Western and immunoprecipitation.
resultsRemarkably, overexpression of FLRF significantly attenuated erythroid and myeloid differentiation of EML cells in response to cytokines erythropoietin (EPO) and interleukin-3 (IL-3), and retinoic acid (RA), and resulted in significant and constitutive decrease of steady-state levels of IL-3, EPO, and RA receptor-alpha (RARalpha) in EML and BaF3 cells. Immunoprecipitation has revealed that FLRF interacts with IL-3, EPO, and RARalpha receptors in EML and BaF3 cells, and that FLRF-mediated downregulation of these receptors is ligand binding-independent.
conclusionsThe results of this study have revealed new FLRF-mediated pathway for ligand-independent receptor level regulation, and support the notion that through maintaining basal levels of cytokine receptors, FLRF is involved in the control of hematopoietic progenitor cell differentiation into myeloerythroid lineages.
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