GATA transcription factors inhibit cytokine-dependent growth and survival of a hematopoietic cell line through the inhibition of STAT3 activity

Sachiko Ezoe, Itaru Matsumura, Karin Gale, Yusuke Satoh, Jun Ishikawa, Masao Mizuki, Satoru Takahashi, Naoko Minegishi, Koichi Nakajima, Masayuki Yamamoto, Tariq Enver, Yuzuru Kanakura

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27 Citations (Scopus)

Abstract

Although GATA-1 and GATA-2 were shown to be essential for the development of hematopoietic cells by gene targeting experiments, they were also reported to inhibit the growth of hematopoietic cells. Therefore, in this study, we examined the effects of GATA-1 and GATA-2 on cytokine signals. A tamoxifen-inducible form of GATA-1 (GATA-1/ERT) showed a minor inhibitory effect on interleukin-3 (IL-3)-dependent growth of an IL-3-dependent cell line Ba/F3. On the other hand, it drastically inhibited TPO-dependent growth and gp130-mediated growth/survival of Ba/F3. Similarly, an estradiol-inducible form of GATA-2 (GATA-2/ER) disrupted thrombopoietin (TPO)-dependent growth and gp130-mediated growth/survival of Ba/F3. As for this mechanism, we found that both GATA-1 and GATA-2 directly bound to STAT3 both in vitro and in vivo and inhibited its DNA-binding activity in gel shift assays and chromatin immunoprecipitation assays, whereas they hardly affected STAT5 activity. In addition, endogenous GATA-1 was found to interact with STAT3 in normal megakaryocytes, suggesting that GATA-1 may inhibit STAT3 activity in normal hematopoietic cells. Furthermore, we found that GATA-1 suppressed STAT3 activity through its N-zinc finger domain. Together, these results suggest that, besides the roles as transcription factors, GATA family proteins modulate cytokine signals through protein-protein interactions, thereby regulating the growth and survival of hematopoietic cells.

Original languageEnglish
Pages (from-to)13163-13170
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number13
DOIs
Publication statusPublished - 2005 Apr 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ezoe, S., Matsumura, I., Gale, K., Satoh, Y., Ishikawa, J., Mizuki, M., Takahashi, S., Minegishi, N., Nakajima, K., Yamamoto, M., Enver, T., & Kanakura, Y. (2005). GATA transcription factors inhibit cytokine-dependent growth and survival of a hematopoietic cell line through the inhibition of STAT3 activity. Journal of Biological Chemistry, 280(13), 13163-13170. https://doi.org/10.1074/jbc.M413461200