Cell Growth & Differentiation, Vol 6, Issue 4 429-437, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Erythropoietin exerts transcriptional and translational control over globin synthesis in J2E cells

SJ Busfield, DS Chappell, G Jennings, NJ Trengove, KJ Riches, BA Callus, PA Tilbrook and SP Klinken
Department of Biochemistry, University of Western Australia, Nedlands.

The J2E erythroid cell line, generated by transforming fetal liver cells, terminally differentiates in response to erythropoietin (epo). The cells expressed both adult and embryonic globin genes, although considerably more adult globin was produced, and transcripts for both species rose following exposure to epo. A 6-fold increase in transcription of the adult alpha and beta maj globin genes was observed after hormonal stimulation, which resulted in a substantial accumulation of mRNA. In addition, a modest but transient rise in translation enabled a 6-fold elevation in globin protein to occur. Concurrently, the total heme content rose markedly, enhancing hemoglobin synthesis 10-fold. The prosthetic group complexed entirely with globin proteins, and the hemoglobin produced was present as fully functional oxyhemoglobin, capable of gaseous exchange. We concluded, therefore, that hemoglobin synthesis in epo-induced J2E cells normally results from the coordinate stimulation of heme and globin synthesis. However, some mutant clones emerged where concomitant increases in globin and heme were not observed. Despite similar profiles for the appearance of hemoglobin and equivalent amounts of the oxygen carrier, several noticeable differences in globin synthesis were detected between epo-induced J2E cells and DMSO-stimulated murine erythroleukemia cells, i.e., the types of globin genes expressed, patterns of mRNA and protein production, and translation rates. These results demonstrate that the J2E cells provide a useful model system for investigating the molecular mechanisms of epo-initiated hemoglobin synthesis.

This article has been cited by other articles:

				A. Spadaccini, P. A. Tilbrook, M. K. Sarna, M. Crossley, J. J. Bieker, and S. P. Klinken Transcription Factor Erythroid Kruppel-like Factor (ELKF) Is Essential for the Erythropoietin-induced Hemoglobin Production but Not for Proliferation, Viability, or Morphological Maturation J. Biol. Chem., September 11, 1998; 273(37): 23793 - 23798. [Abstract] [Full Text] [PDF]

				M. S. Sayer, P. A. Tilbrook, A. Spadaccini, E. Ingley, M. K. Sarna, J. H. Williams, N. C. Andrews, and S. P. Klinken Ectopic Expression of Transcription Factor NF-E2 Alters the Phenotype of Erythroid and Monoblastoid Cells J. Biol. Chem., August 11, 2000; 275(33): 25292 - 25298. [Abstract] [Full Text] [PDF]