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  • The EMBO Journal (2000) 19, 5845 - 5855
  • doi:10.1093/emboj/19.21.5845

The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3

Bernd Rödel1,6, Kamiab Tavassoli1,6, Holger Karsunky1, Thorsten Schmidt2, Malte Bachmann1, Fred Schaper3, Peter Heinrich3, Ke Shuai4, Hans Peter Elsässer5 and Tarik Möröy1

  1. Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, D-45122 Essen, Germany
  2. Bayer AG, Apratherweg 18a, D-42096 Wuppertal, Germany
  3. Institut für Biochemie, Universitätsklinikum, RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
  4. Division of Hematology/Oncology, UCLA School of Medicine, Los Angeles, CA, USA
  5. Institut für Zytobiologie und Zytopathologie, Philipps Universität Marburg, D-35033 Marburg, Germany
  6. B.Rödel and K.Tavassoli contributed equally to this work

Correspondence to:

Tarik Möröy, E-mail: moeroey@uni-essen.de

Received 20 June 2000; Accepted 12 September 2000; Revised 28 August 2000

STAT factors act as signal transducers of cytokine receptors and transcriptionally activate specific target genes. The recently discovered protein PIAS3 binds directly to STAT3 and blocks transcriptional activation. Here, we present experimental evidence implementing the zinc finger protein Gfi-1 as a new regulatory factor in STAT3-mediated signal transduction. The interaction between the two proteins first became evident in a yeast two-hybrid screen but was also seen in coprecipitation experiments from eukaryotic cells. Moreover, we found that both Gfi-1 and PIAS3 colocalize in a characteristic nuclear dot structure. While PIAS3 exerts a profound inhibitory effect on STAT3-mediated transcription of target promoters, Gfi-1 can overcome the PIAS3 block and significantly enhances STAT3-mediated transcriptional activation. In primary T cells, Gfi-1 was able to amplify IL-6-dependent T-cell activation. As Gfi-1 is a known, dominant proto-oncogene, our findings bear particular importance for the recently described ability of STAT3 to transform cells malignantly and offer an explanation of the oncogenic potential of Gfi-1 in T lymphocytes.

  • Keywords:

    • cytokine signaling,
    • Gfi-1,
    • nuclear dots,
    • STAT3,
    • T-cell proliferation