ERF, an ETS-related transcriptional repressor, can induce erythroid differentiation.
Ets-family genes have been implicated in leukemia, as well as in normal hematopoiesis. ERF is an ets-related gene that represses transcription and is regulated by MAPK phosphorylation through its effect on ERF sub-cellular localization. Using pluripotent human cell lines, we studied the effect of ERF on erythroid differentiation. K562 and HEL cells expressing ERF expressed elevated levels of the erythroid-specific markers CD71 and Glycophorin A, as well as hemoglobin and GATA1. Treatment with the Erk kinase inhibitor PD98058 further enhanced the erythroid phenotype in ERF-expressing cells and cells expressing a non-phosphorylatable ERF mutant exhibited an even more enhanced phenotype. These results are consistent with the fact that ERF function is regulated by MAPK, and suggest that the effect of the MAPK pathway in erythroid differentiation is partially mediated by ERF. The effect of ERF is similar to the one shown for ETS1 and opposite to the FLI1 function in these cells, suggesting that several ets genes may play key roles in hematopoietic differentiation.
Athanasiou
Meropi
M
Basic Research Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD 21702, USA. athanasi@ncifcrf.gov
Blair
Donald G
DG
Mavrothalassitis
George
G
D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004920:Erythropoiesis / Q000502:physiology*; D006021:Glycophorins / Q000096:biosynthesis; D006801:Humans; D020014:K562 Cells; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009930:Organic Chemicals; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011990:Receptors, Transferrin; D012097:Repressor Proteins; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D018631:ras Proteins / Q000502:physiology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494069:ETS2 protein, human; D004791:Enzyme Inhibitors; D006021:Glycophorins; D009930:Organic Chemicals; C466090:PD 98058; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D011990:Receptors, Transferrin; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins