SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription

Hideaki Nakajima, Toshiki Tamura, Miyuki Ito, Fumi Shibata, Kana Kuroda, Yumi Fukuchi, Naohide Watanabe, Toshio Kitamura, Yasuo Ikeda, Makoto Handa

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4 Citations (Scopus)

Abstract

STAT5 is a critical mediator of a variety of cytokine signaling whose transcriptional activity is regulated by associating with various proteins. During a search for STAT5-interacting proteins, we identified SHD1, a mammalian homologue of yeast gene Sac3, as a potential interacter. SHD1 was localized in the nucleus, and induced by cytokines that activate STAT5, such as erythropoietin, interleukin-2 (IL-2), or IL-3. SHD1 interacted specifically with STAT5A and STAT5B, and interestingly, it specifically repressed STAT5-dependent transcription in vitro without affecting the stability or phosphorylation of STAT5 protein. Gene disruption study revealed that T, B, or bone marrow cells from mice lacking SHD1 were hyperresponsive to T-cell-receptor engagement, or stimulation with various STAT5-activating cytokines. These results suggest that SHD1 is a novel cytokine-inducible negative feedback regulator of STAT5.

Original languageEnglish
Pages (from-to)1027-1036
Number of pages10
JournalBlood
Volume113
Issue number5
DOIs
Publication statusPublished - 2009 Jan 29

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Nakajima, H., Tamura, T., Ito, M., Shibata, F., Kuroda, K., Fukuchi, Y., Watanabe, N., Kitamura, T., Ikeda, Y., & Handa, M. (2009). SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription. Blood, 113(5), 1027-1036. https://doi.org/10.1182/blood-2008-01-133405