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J Biol Chem, Vol. 274, Issue 18, 12910-12916, April 30, 1999
Regulation of the Human Interleukin-5 Promoter by Ets
Transcription Factors
ETS1 AND ETS2, BUT NOT ELF-1, COOPERATE WITH GATA3 AND HTLV-I
TAX1
Sibylle G.
Blumenthal ,
Gabriele
Aichele ,
Thomas
Wirth§,
Armin P.
Czernilofsky¶,
Alfred
Nordheim , and
Jürgen
Dittmer
From the Institut für Zellbiologie, Abteilung
Molekularbiologie, Universität Tübingen, Auf der
Morgenstelle 15, 72076 Tübingen, Germany, the
§ Institut für Medizinische Strahlenkunde und
Zellforschung (MSZ), Versbacher Strasse 5, 97078 Würzburg,
Germany, and the ¶ Bender + Co Gesellschaft mbH, Dr.
Boehringer-Gasse 5-11, 1121 Wien, Austria
Interleukin-5 (IL-5), expressed primarily by
type-2 T helper (Th2) cells, plays an important role in the development
of allergic diseases, such as allergic asthma. Studying the regulation
of IL-5 gene expression by Ets transcription factors, we found that Ets1 and Ets2, but not Elf-1, were able to activate the human IL-5
promoter in Jurkat T-cells. This required the presence of either
phorbol 12-myristate acetate (PMA) plus ionomycin or PMA plus the viral
protein HTLV-I Tax1. By mutation studies, it could be
shown that Ets1 and Ets2 exerted their effects on the IL-5 promoter
through a GGAA motif within the Cle0 element. In myeloid Kasumi cells,
Ets1 and Ets2 failed to stimulate IL-5 promoter activity, unless the
T-cell specific transcription factor GATA3 was added. These results
show, for the first time, that Ets1 and Ets2 are able to cooperate with
GATA3. Both ionomycin and Tax1 increased the combined
effect of GATA3 with Ets1 and Ets2 in the presence of PMA. The data
further demonstrate that, in addition to Ets1, Ets2 is also able to
functionally cooperate with Tax1. The synergism of GATA3
with either Ets1 or Ets2 may play an important role in calcium- or
Tax1-dependent regulation of IL-5 expression in
Th2 cells or in HTLV-I transformed adult T-cell leukemia cells, respectively.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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