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Tieg3/Klf11 induces apoptosis in OLI‐neu cells and enhances the TGF‐β signaling pathway by transcriptional repression of Smad7
Author(s) -
Gohla Gabriele,
Krieglstein Kerstin,
Spittau Björn
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21669
Subject(s) - microbiology and biotechnology , smad , psychological repression , crosstalk , signal transduction , transcription factor , r smad , biology , transforming growth factor , apoptosis , programmed cell death , cell signaling , chemistry , genetics , gene expression , endoglin , gene , stem cell , physics , cd34 , optics
TGF‐β signaling is indispensible for development of the nervous system since it regulates ontogenetic cell death. The recently identified TGF‐β‐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‐β‐responsive oligodendroglial cell line OLI‐neu, we analyzed the role of Tieg3/Klf11 in TGF‐β signaling. In this report, we show that Tieg3/Klf 11 mimics TGF‐β effects by inducing apoptotic cell death accompanied by activation of caspase‐3. Moreover, we demonstrate that Tieg3/Klf11 enhances TGF‐β signaling by transcriptional repression of the inhibitory Smad7 and, thereby, disrupts the negative feedback loop of the TGF‐β 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‐β responses. In conclusion, we provide evidence that the recently identified transcription factor Tieg3/Klf11 is a downstream mediator of TGF‐β‐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‐β signaling by transcriptional inhibition of Smad7 might be an important clue for the understanding of the crosstalk between different signaling pathways. J. Cell. Biochem. 104: 850–861, 2008. © 2008 Wiley‐Liss, Inc.