Human TIEG2/KLF11 induces oligodendroglial cell death by downregulation of Bcl-XL expression.
TGF-beta-induced apoptosis is essential for embryonic development and mainteanance of adult tissues. Impairment of the apoptotic pathway, regulated by TGF-beta, plays a center role in tumorigenesis and manifestations of different diseases. TIEG2/KLF11 is a recently identified human TGF-beta-inducible zinc finger protein belonging to the family of Sp1/KLF-like transcription factors. In human and murine tissues it has been shown that TIEG1 and TIEG2 induce apoptosis and inhibit cell growth. Since TGF-beta and Tieg1 are able to induce apoptosis in the oligodendroglial cell line OLI-neu, we analysed the ability of TIEG2 to mimic the effects observed after treatment with TGF-beta and overexpression of Tieg1. Herein we report that TIEG2 induces Caspase3-dependent apoptosis in murine OLI-neu cells. Furthermore, we could demonstrate that TIEG2 decreases the levels of the anti-apoptotic protein Bcl-X(L) and inhibits transcription driven by the Bcl-X(L) promoter. These data suggest that TIEG2 serves as a downstream mediator of TGF-beta, bridging TGF-beta-dependent signaling to the intracellular pathway of apoptosis.
Wang
Z
Z
Center of Anatomy, Department of Neuroanatomy, University of Goettingen, Goettingen, Germany.
Spittau
B
B
Behrendt
M
M
Peters
B
B
Krieglstein
K
K
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016923:Cell Death / Q000235:genetics; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C115117:KLF11 protein, human; D012097:Repressor Proteins; D051020:bcl-X Protein