Topic
NFE2
About: NFE2 is a research topic. Over the lifetime, 10 publications have been published within this topic receiving 932 citations. The topic is also known as: NF-E2 & p45.
Papers
TL;DR: It is proposed that the mk mutation results in an impaired form of NF-E2 which fails to regulate both globin production and iron metabolism properly.
Abstract: The nuclear DNA-binding protein NF-E2 is thought to mediate the powerful erythroid enhancer activity of the alpha- and beta-globin locus control regions and participates in the control of genes encoding two enzymes of haem biosynthesis (porphobilinogen deaminase and ferrochelatase) The major component of NF-E2 is a 45K polypeptide (designated p45 NF-E2) that belongs to the basic region-leucine zipper family of transcription factors This subunit of NF-E2 is specifically expressed in haematopoietic progenitor cells and differentiated cells of the erythroid, megakaryocyte and mast cell lineages The gene encoding p45 NF-E2 (murine gene Nfe2) has been mapped to mouse chromosome 15 near the mutation microcytosis (mk) Homozygous mk mice have severe hypochromic microcytic anaemia as a result of decreased globin synthesis and defects in intestinal and erythroid iron absorption Here we investigate whether the mk mutation lies within Nfe2 by characterizing the p45 NF-E2 gene and determining its DNA sequence in wild-type and mk alleles The mk allele carries a missense mutation that causes substitution of valine by alanine at amino acid 173 of the p45 NF-E2 protein Expression of p45 NF-E2 messenger RNA was detected in erythroid tissues of normal mice and in the duodenum of normal and severely anaemic beta-thalassaemic (Hbbd-th3/Hbbd-th3) mice We propose that the mk mutation results in an impaired form of NF-E2 which fails to regulate both globin production and iron metabolism properly
55 citations
TL;DR: These data indicate that in vitro liquid cultures of committed CD36+ erythroid progenitor cells retain, in part, many features of erythropoiesis at the cellular and molecular level and may provide a useful model for assessment of disease-related or drug-induced ERYthropoietic abnormalities.
48 citations
TL;DR: It is shown that Nfe2 represses JunD DNA-binding activity to the Gcm1 promoter during syncytiotrophoblast differentiation, identifying a novel mechanism through which bZip transcription factors interact within the placenta.
20 citations
TL;DR: This review describes the electrophilic and non-electrophilic NRF2 activators with clinical projection in various chronic diseases and analyzes the status ofNRF2 inhibitors, which are for the moment in a proof-of-concept stage.
Abstract: The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) triggers homeostatic responses against a plethora of environmental or endogenous deviations in redox metabolism, inflammation, proteostasis, etc. Therefore, pharmacological activation of NRF2 is a promising therapeutic strategy for several chronic diseases that are underlined by low-grade oxidative inflammation and dysregulation of redox metabolism, such as neurodegenerative, cardiovascular, and metabolic diseases. While NRF2 activation is useful in inhibiting carcinogenesis, its inhibition is needed in constituted tumors where NRF2 provides a survival advantage in the challenging tumor niche. This review describes the electrophilic and non-electrophilic NRF2 activators with clinical projection in various chronic diseases. We also analyze the status of NRF2 inhibitors, which are for the moment in a proof-of-concept stage. Advanced in silico screening and medicinal chemistry are expected to provide new or repurposing small molecules with increased potential for fostering the development of targeted NRF2 modulators. The nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2) is rapidly degraded by proteasomes under a basal condition in a Keap1-dependent manner. ROS oxidatively modifies Keap1 to release NRF2 and allow its nuclear translocation. Here it binds to the antioxidant response element to regulate gene transcription. An alternative mechanism controlling NRF2 stability is glycogen synthase kinase 3 (GSK-3)-induced phosphorylation. Indicated in blue are NRF2-activating and NRF2-inhibiting drugs.
19 citations
TL;DR: It is shown that unlike mammals, zebrafish survive to adulthood in the absence of Nfe2, and the data suggest parallels with erythropoiesis, including distinct primitive and definitive pathways of development and potential for a previously unknown NFE2-independent pathway of embryonic thrombopoiedis.
13 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2020 | 2 |
| 2016 | 2 |
| 2014 | 1 |
| 2013 | 1 |
| 2012 | 1 |
| 2003 | 1 |