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J Biol Chem, Vol. 273, Issue 33, 20779-20784, August 14, 1998
From the The STAT5 activation has important roles in cell
differentiation, cell cycle control, and development. However, the
potential implications of STAT5 in the control of apoptosis remain
unexplored. To evaluate any possible link between the erythropoietin
receptor (EpoR) JAK2/STAT5 transduction pathway and apoptosis, we have investigated apoptosis-resistant cells (ApoR) that arose from positive
selection of the erythroid-committed Ba/F3EpoR cells triggered to
apoptosis by ectopic expression of the HOX-B8 homeotic gene. We show
that JAK2 is normally activated by Epo in both Ba/F3EpoR and ApoR
cells. In contrast, both STAT5a and STAT5b isoforms are uniquely
activated in a C-truncated form (86 kDa) only in ApoR cells. Analysis
of ApoR and Ba/F3EpoR subclones confirmed that the switch to the
truncated STAT5 isoform coincides with apoptosis survival and that ApoR
do not derive from preexisting cells with a shortened STAT5. In
addition, ApoR cells die in the absence of Epo. This indicates that
resistance to apoptosis is not because of a general defect in the
apoptotic pathway of ApoR cells. Furthermore, we show that the 86-kDa
STAT5 protein presents a dominant-negative (DN) character. We
hypothesize that the switch to a DN STAT5 may be part of a mechanism
that allows ApoR cells to be selectively advantaged during apoptosis.
In conclusion, we provide evidence for a functional correlation between
a naturally occurring DN STAT5 and a biological response.
Positive Selection of Apoptosis-resistant Cells Correlates with
Activation of Dominant-Negative STAT5
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Institutes of Biological Chemistry and
¶ Anatomy, Institute for Neurological Sciences "C. Besta",
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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