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Induction of sequence-specific DNA-binding factors by erythropoietin and
the spleen focus-forming virus
T Ohashi, M Masuda and SK Ruscetti
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, MD
21702-1201.
The signal transduction mechanism of erythropoietin (Epo), which regulates
growth and differentiation of erythroid cells, is still unclear. Recent
studies showing the activation by various ligands of a group of proteins
called Stat (signal transducers and activators of transcription) proteins
raised the possibility that such proteins may also be involved in the Epo
signal transduction pathway. In this report, we show that Epo induces
factors that specifically bind to the sis-inducible element and the gamma
response region of the Fc gamma receptor factor I gene in the Epo-dependent
mouse erythroleukemia cell line HCD-57. These factors contain
phosphotyrosine and antibodies against Stat1 and Stat3 proteins reacted
with them. In HCD-57 cells infected with Friend spleen focus-forming virus,
which now grow in an Epo-independent manner, the DNA-binding factors were
constitutively activated even in the absence of Epo. These results suggest
that the factors induced by Epo contain components identical or related to
known Stat proteins. It is also suggested that continuous activation of
these DNA-binding factors may be responsible for the ability of spleen
focus- forming virus to abrogate the Epo-dependence of HCD-57 cells and
cause erythroleukemia in susceptible mice.
Volume 85,
Issue 6,
pp. 1454-1462,
03/15/1995
Copyright © 1995 by The American Society of Hematology
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