Erythroid transcription factor NF-E2 is a haematopoietic-specfic basic-leucine zipper protein

Harvard University, Cambridge, Massachusetts, United States
Nature (Impact Factor: 41.46). 05/1993; 362(6422):722-8. DOI: 10.1038/362722a0
Source: PubMed

ABSTRACT Expression of globin genes in developing erythroid cells is controlled by upstream locus control regions. Activity of these regions in vivo requires an erythroid-specific nuclear factor (NF-E2) that binds AP-1-like recognition sites. Its tissue-specific component (p45 NF-E2) has been characterized by complementary DNA cloning as a new basic region-leucine zipper protein which dimerizes with a ubiquitous partner to form native NF-E2.

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Available from: Hediye Erdjument-Bromage, May 01, 2015
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    • "The expression of antioxidant cytoprotective genes is controlled primarily by the cap‘n’collar (CNC) family of transcription factors12. This family comprises the Drosophila Cnc protein as the founding member34, the Caenorhabditis elegans protein skinhead-1 (Skn-1)56, and four vertebrate activators nuclear factor-erythroid 2 (NF-E2) p45 subunit789, NF-E2 p45-related factor 1 [Nrf1 (ref. 10), including its long form, called transcription factor 11 (TCF11)1112 and its short isoform, designated as locus control region-factor 1 (LCR-F1)1314, see Fig. 1], Nrf2 (ref. "
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    ABSTRACT: The integral membrane-bound Nrf1 transcription factor fulfils important functions in maintaining cellular homeostasis and organ integrity, but how it is controlled vectorially is unknown. Herein, creative use of Gal4-based reporter assays with protease protection assays (GRAPPA), and double fluorescence protease protection (dFPP), reveals that the membrane-topogenic vectorial behaviour of Nrf1 dictates its post-translational modification and transactivation activity. Nrf1 is integrated within endoplasmic reticulum (ER) membranes through its NHB1-associated TM1 in cooperation with other semihydrophobic amphipathic regions. The transactivation domains (TADs) of Nrf1, including its Asn/Ser/Thr-rich (NST) glycodomain, are transiently translocated into the ER lumen, where it is glycosylated in the presence of glucose to become a 120-kDa isoform. Thereafter, the NST-adjoining TADs are partially repartitioned out of membranes into the cyto/nucleoplasmic side, where Nrf1 is subject to deglycosylation and/or proteolysis to generate 95-kDa and 85-kDa isoforms. Therefore, the vectorial process of Nrf1 controls its target gene expression.
    Scientific Reports 06/2013; 3(2006):1-16. DOI:10.1038/srep02006 · 5.58 Impact Factor
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    • "NFE2 is expressed in hematopoietic progenitor cells as well as in the myeloid, erythroid and MK lineages 98. NFE2 knock-out mice completely lack circulating platelets. "
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    ABSTRACT: Cell type-specific transcription factors regulate the repertoire of genes expressed in a cell and thereby determine its phenotype. The differentiation of megakaryocytes, the platelet progenitors, from haematopoietic stem cells is a well known process that can be mimicked in culture. However, the efficient formation of platelets in culture remains a challenge. Platelet formation is a complicated process including megakaryocyte maturation, platelet assembly and platelet shedding. We hypothesise that a better understanding of the transcriptional regulation of this process will allow us to influence it such that sufficient numbers of platelets can be produced for clinical applications. After an introduction to gene regulation and platelet formation, this review summarises the current knowledge on the regulation of platelet formation by the transcription factors EVI1, GATA1, FLI1, NFE2, RUNX1, SRF and its co-factor MKL1, and TAL1. Also covered is how some platelet disorders including myeloproliferative neoplasms, result from disturbances of the transcriptional regulation. These disorders give us invaluable insights in the crucial role these transcription factors play in platelet formation. Finally, it is discussed how a better understanding of these processes will be needed to allow for efficient production of platelets in vitro. © 2013 International Society on Thrombosis and Haemostasis.
    Journal of Thrombosis and Haemostasis 01/2013; 11(4). DOI:10.1111/jth.12131 · 5.72 Impact Factor
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    • "Nuclear factor erythroid-derived 2-related factor 1 (Nrf1) is a member of the Cap ‘n’Collar (CNC) family of transcription factors that includes 3 closely related members, Nrf2, Nrf3, and p45NFE2 [1], [2], [3], [4]. These CNC members contain a conserved basic-leucine-zipper (bZIP) domain known to heterodimerize with small Maf oncoproteins (MafF, MafG, MafK) and bind to cis-acting sequences [5]. "
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    ABSTRACT: Nuclear factor E2-related factor 1 (Nrf1) is a basic leucine zipper transcription factor that plays an important role in the activation of cytoprotective genes through the antioxidant response elements. The previously characterized long isoform of Nrf1 (Nrf1a) is targeted to the endoplasmic reticulum and accumulates in the nucleus in response to activating signals. Here we characterized a novel Nrf1 protein isoform (Nrf1b) generated through an alternative promoter and first exon that lacks the ER targeting domain of Nrf1a. The 5'-flanking region of Nrf1b directed high levels of luciferase reporter expression in cells. RT-PCR and Western blotting showed Nrf1b is widely expressed in various cell lines and mouse tissues. Immunoblot analysis of subcellular fractions and imaging of green fluorescence protein (GFP)-tagged Nrf1b demonstrate Nrf1b is constitutively localized to the nucleus. Nrf1b can activate GAL4-dependent transcription when fused to the heterologous GAL4 DNA-binding domain. Gel-shift and coimmunoprecipitation experiments demonstrate that Nrf1b forms a complex with MafG, and expression of Nrf1b activates the expression of antioxidant response element containing reporters and genes in cells. These results suggest Nrf1b is targeted to the nucleus where it activates ARE-driven genes and may play a role in modulating antioxidant response elements.
    PLoS ONE 10/2012; 7(10):e48404. DOI:10.1371/journal.pone.0048404 · 3.23 Impact Factor
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