Tieg3/Klf11 induces apoptosis in OLI-neu cells and enhances the TGF-beta signaling pathway by transcriptional repression of Smad7.

TGF-beta signaling is indispensible for development of the nervous system since it regulates ontogenetic cell death. The recently identified TGF-beta-inducible zinc finger protein Tieg3/Klf11 belongs to the family of Sp1/Klf-like transcription factors and shares all structural and functional features with other Tieg proteins. Using the established TGF-beta-responsive oligodendroglial cell line OLI-neu, we analyzed the role of Tieg3/Klf11 in TGF-beta signaling. In this report, we show that Tieg3/Klf 11 mimics TGF-beta effects by inducing apoptotic cell death accompanied by activation of caspase-3. Moreover, we demonstrate that Tieg3/Klf11 enhances TGF-beta signaling by transcriptional repression of the inhibitory Smad7 and, thereby, disrupts the negative feedback loop of the TGF-beta signaling pathway. Loss of the N-terminal repression domains of Tieg3/Klf11 abrogates the pro-apoptotic nature of this transcription factor and abolishes the enhancement of Smad-mediated TGF-beta responses. In conclusion, we provide evidence that the recently identified transcription factor Tieg3/Klf11 is a downstream mediator of TGF-beta-induced apoptosis in the oligodendroglial cell line OLI-neu. Since other signaling molecules are able to initiate transcription of members of the Tieg family, the ability of Tieg3/Klf11 to modulate TGF-beta signaling by transcriptional inhibition of Smad7 might be an important clue for the understanding of the crosstalk between different signaling pathways.