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

STAT factors act as signal transducers of cytokine receptors and transcript ionally activate specific target genes. The recently discovered protein PIA S3 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 interac tion between the two proteins first became evident in a yeast two-hybrid sc reen but was also seen in coprecipitation experiments from eukaryotic cells . Moreover, we found that both Gfi-1 and PIAS3 colocalize in a characterist ic nuclear dot structure. While PIAS3 exerts a profound inhibitory effect o n STAT3-mediated transcription of target promoters, Gfi-1 can overcome the PIAS3 block and significantly enhances STAT3-mediated transcriptional activ ation. 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 trans form cells malignantly and offer an explanation of the oncogenic potential of Gfi-1 in T lymphocytes.