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Moreover, it is suggested that the increase of EPOR mRNA expression at the
resting phase induced by growth factor starvation is dependent on other tran-
scription factors than GATA-1 (Fig. 3) [72]. Furthermore, in a human EPO-
independent acute megakaryoblastic leukemia cell line (HML/SE), SCF
induces
EPOR
gene expression by activating its promoter [73]. Human
EPOR
gene expression can also be significantly upregulated by IL-1
and the trans-
lation inhibitor cycloheximide [74]. Moreover, it has been shown that IFN-
α
γ
down-regulates EPOR at the surface of erythroid progenitor cells, and the
resulting inactivation of EPOR might reduce survival of these cells and induce
apoptosis [75]. At the post-transcriptional level, EPOR expression can be reg-
ulated by chemical agents such as phorbol myristate acetate [64]. Post-trans-
lational modification of the EPOR is reported in IL-3 dependent (murine) cell
lines [66].
Figure 3. Model for relation between EPOR and GATA-1 expression during the cell cycle in human
EPO-dependent hematopoietic progenitor cells. EPOR expression in the proliferating cell is mediat-
ed at the level of transcription through cell cycle-dependent GATA-1 expression. However, in the qui-
escent phase other factors appear to regulate EPOR expression. (From [72] with permission.)
Effects of EPOR activation on the expression pattern of other genes
Signals from EPOR activate genes that are important in cell proliferation, dif-
ferentiation, or survival. They include GATA-2,
c-myc
,
c-myb
,and
c-Fos/c-Jun
(only in murine EPO-dependent cells) as regulators of proliferation [25,
76-78]. Bcl-x
L
and Bcl-2 are activated as antiapoptotic genes [79]. However,
in a human EPO-dependent erythroid cell line (AS-E2), EPOR signals also
negatively regulate GATA-1,
c-myb
,
-globin,
-globin, and
β
-globin [25].
α
γ
