TIEG1 facilitates transforming growth factor-beta-mediated apoptosis in the oligodendroglial cell line OLI-neu.
Transforming growth factor-beta (TGF-beta) plays an important role during the period of developmental cell death in the nervous system. Using the oligodendroglial precursor cell line OLI-neu, we have previously established an in vitro system to analyze TGF-beta-mediated cell death on the molecular level. We could show that the Krüppel-like Zn-finger transcription factor TIEG1 was up-regulated after TGF-beta stimulation of OLI-neu cells and mimicked TGF-beta effects in these cells; i.e., overexpression of TIEG1 in OLI-neu cells induced apoptosis as shown by apoptosis ELISA, DNA fragmentation, and caspases-3 activation. The apoptotic pathway seemed to be initiated by repressing the expression of the antiapoptotic protein Bcl-XL. In contrast, the reporter activity of a SMAD consensus promoter was induced, whereas the promoter activity of the inhibitory SMAD7 was reduced, suggesting that SMAD-dependent TGF-beta responses, such as TGF-beta-induced apoptosis, are enhanced in the presence of TIEG1.
Bender
Herdis
H
Center of Anatomy, University of Goettingen, Goettingen, Germany.
Wang
Ziyuan
Z
Schuster
Norbert
N
Krieglstein
Kerstin
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology*; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051785:Smad Proteins; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation; D051020:bcl-X Protein; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D053148:Caspase 3; D020169:Caspases; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051785:Smad Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051020:bcl-X Protein; C494812:Bcl2l1 protein, mouse; C090468:TP53BP2 protein, human; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C569958:KLF10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors