Erythropoietin Receptor Binds to Friend Virus GP55 through Other Membrane Components

Kishi, Anna; Chiba, T.; Sugiyama, Michio; Machide, Mitsuru; Nagata, Yoshihiko; Arima, Hiroshi; Taira, Hideharu; Katsumata, Teizo; Todokoro, Kazuo

doi:10.1006/bbrc.1993.1534

Cited by 11 publications

(7 citation statements)

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“…DS cells undergo erythroid differentiation after treatment with Me 2 SO and express erythroid markers such as ␤-globin (19,20), heme pathway enzymes (18,21), and erythropoietin receptor (22,23); they ultimately cease to grow in culture after a few days by completing differentiation (24). In contrast, DR cells fail to show terminal erythroid differentiation when treated with Me 2 SO, and they continue to grow as hemoglobin-free cells in culture (17).…”

Section: Methodsmentioning

confidence: 99%

Regulation of NF-E2 Activity in Erythroleukemia Cell Differentiation

Nagai¹,

Igarashi²,

Akasaka³

et al. 1998

Journal of Biological Chemistry

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The erythroid transcription factor NF-E2 is an obligate heterodimer composed of two different subunits (p45 and p18), each containing a basic region-leucine zipper DNA binding domain, and it plays a critical role in erythroid differentiation as an enhancer-binding protein for expression of the ␤-globin gene. We show here that dimethyl sulfoxide treatment of wild-type murine erythroleukemia cells, but not a mutant clone of dimethyl sulfoxide-resistant cells, increases NF-E2 activity significantly, which involves both up-regulation of DNA binding and transactivation activities. Both activities were reduced markedly by treatment of cells with 2-aminopurine but not by genistein. Activation of the Ras-Raf-MAP kinase signaling cascade increased NF-E2 activity significantly, but this was suppressed when MafK was overexpressed. Domain analysis revealed an activation domain in the NH 2 -terminal region of p45 and a suppression domain in the basic region-leucine zipper of MafK. These findings indicate that induction of NF-E2 activity is essential for erythroid differentiation of murine erythroleukemia cells, and serine/threonine phosphorylation may be involved in this process. In addition, they also suggest that a MafK homodimer can suppress transcription, not only by competition for the DNA binding site, but also by direct inhibition of transcription. Hence, MafK may function as an active transcription repressor.The erythroid transcription factor NF-E2 is present in extracts of erythroid cell lines (1, 2) and has been shown to be a heterodimer formed between the two basic region-leucine zipper (b-zip) 1 proteins, i.e. the p45 and the p18 subunits. p45, which together with the Drosophila cap'n-collar (CNC) protein defines a b-zip subfamily, is expressed in hematopoietic cells of the erythroid, megakaryocytic, and mast cell lineages (1), whereas p18 is one of the small Maf family proteins including MafK 2 (1-4), and its expression is not restricted to hematopoietic cells (5). Involvement of NF-E2 in erythroid cell differentiation of mouse erythroleukemia (MEL) cells has been suggested by its role as an enhancer-binding protein for expression of the ␤-globin gene, by the lack of ␤-globin mRNA expression in a MEL cell line (CB3) devoid of NF-E2 protein as a result of integration of Friend viral sequences within the p45 NF-E2 gene locus (6), and by the restoration of ␤-globin mRNA by forced expression of p45 cDNA in these cells (6, 7). It has also been found that NF-E2⅐DNA binding increases during erythroid differentiation of MEL cells (8 -10). These results suggest NF-E2 to be one of the key transcription factors that regulate erythroid differentiation of MEL cells. Unexpectedly, targeted disruption of the p45 gene in mice showed essentially no abnormality in erythropoiesis (11,12). It is possible in these conditions, however, that p45-related b-zip factors, such as Nrf1 (13), or Nrf2 (14), may compensate for deficient NF-E2 activity.Previous studies showed that p45 can be phosphorylated by a cAMP-dependent protein kinase in...

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Section: Methodsmentioning

confidence: 99%

Regulation of NF-E2 Activity in Erythroleukemia Cell Differentiation

Nagai¹,

Igarashi²,

Akasaka³

et al. 1998

Journal of Biological Chemistry

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“…Although this system provides a powerful means to detect activation of EpoR by viral-encoded glycoproteins (13,18,26,28,30,33,55,62,64), our results suggest that it has several limitations that must be considered, especially in interpreting negative data. For example, in carefully controlled studies, it is clear that hEpoR is reproducibly highly resistant to activation by gp55 (Table 3).…”

Section: Discussionmentioning

confidence: 91%

“…Thus, assay results may depend to some extent on the passage and selection history of the cells and on the experimental outcomes that are scored as positive. Previous investigators concluded that BaF3-hEpoR cells did (26) or did not (55) become factor independent after SFFV infections.…”

Section: Discussionmentioning

confidence: 99%

“…This strongly suggests that a factor(s) in the BaF3 cytosol that interacts differently with hEpoR and mEpoR can critically affect activation by gp55. Compatible evidence was recently derived from studies of mEpoR-IL-3 receptor and mEpoR-IL-2 receptor chimeras (26).…”

Section: Discussionmentioning

confidence: 99%

“…mEpoR and hEpoR contain 507 and 508 amino acids, respectively, and they are 76% identical in sequence (12,24). Mouse BaF3 cells were used for this analysis because they have been employed for previous studies of SFFV and EpoR (13,18,26,28,30,33,55,62,64), they are from a susceptible strain of mice, and they spontaneously convert to growth factor independence at a negligibly low rate (18,28). Comparable cells are not available from Fv-2 r homozygous mice.…”

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confidence: 99%

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Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia

Hoatlin

Ferro

Geib

et al. 1995

J Virol

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Although the Friend virus-encoded membrane glycoprotein (gp55) activates erythropoietin receptors (EpoR)to cause erythroblastosis only in certain inbred strains of mice but not in other species, mutant viruses can overcome aspects of mouse resistance. Thus, mice homozygous for the resistance allele of the Fv-2 gene are unaffected by gp55 but are susceptible to mutant glycoproteins that have partial deletions in their ecotropic domains. These and other results have suggested that proteins coded for by polymorphic Fv-2 alleles might directly or indirectly interact with EpoR and that changes in gp55 can overcome this defense. A new viral mutant with an exceptionally large deletion in its ecotropic domain is now also shown to overcome Fv-2 rr resistance. In all cases, the glycoproteins that activate EpoR are processed to cell surfaces as disulfide-bonded dimers. To initiate analysis of nonmurine resistances, we expressed human EpoR and mouse EpoR in the interleukin 3-dependent mouse cell line BaF3 and compared the abilities of Friend virus-encoded glycoproteins to convert these cells to growth factor independence. Human EpoR was activated in these cells by erythropoietin but was resistant to gp55. However, human EpoR was efficiently activated in these cells by the same viral mutants that overcome Fv-2 rr resistance in mice. By construction and analysis of human-mouse EpoR chimeras, we obtained evidence that the cytosolic domain of human EpoR contributes to its resistance to gp55 and that this resistance is mediated by accessory cellular factors. Aspects of host resistance in both murine and nonmurine species are targeted specifically against the ecotropic domain of gp55.

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