Untersuchungen zur Rolle von Klf10 und Klf11 als Mediatoren von NGF- und TGF-β-vermittelten Effekten in Zellen neuraler Herkunft

Investigations into the role of Klf10 and Klf11 as mediators of NGF- and TGF-beta-mediated effects in cells of neural origin

by Gabriele Spittau
Doctoral thesis
Date of Examination:2011-11-17
Date of issue:2012-11-15
Advisor:Prof. Dr. Dr. Bertram Brenig
Referee:Prof. Dr. Dr. Bertram Brenig
Referee:Prof. Dr. Christoph Knorr
Referee:Prof. Dr. Kerstin Krieglstein
Persistent Address: http://dx.doi.org/10.53846/goediss-1948

 

 

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Abstract

English

The TGF-β1/Klf-family of transcription factors. They play important roles in development and maintenance of various tissues and cell types. The publications consolidated in this thesis describe, that Klf11 mimics TGF-β effects by inducing apoptotsis accompanied by activation of cysteine-dependent aspartate-specific protease 3 (Caspase-3). Further the thesis demonstrates that Klf11 represses the expression of the inhibitory Sma and Mad related protein 7 (Smad7) and disrupts the negative-feedback loop of the TGF-β signaling pathway. Loss of the N-terminal repression domains of Klf11 abrogates its proapoptotic nature and the repression of Smad7. In conclusion, the evidence was given that the transcription factor Klf11 is a downstream mediator of TGF-β-induced apoptosis and a potent modulator of the TGF-β signaling pathway in the oligodendroglial cell line Oli-neu. In a second part of this thesis it has been shown by using semiquantitative PCR and immunoblotting, that nerve growth factor (NGF), a member of the neurotrophin family, regulates the expression of Klf10 in the pheochromocytoma cell line PC12 in a tropomyosin related kinase A- (TrkA) dependent manner. Moreover, the thesis provides evidence for the existence of NGF-responsive elements in the 5
Keywords: Klf10; KLF11; Sp1-/Krüppelähnliche transcription factors; apoptosis; cell cycle arrest; TGF-β; NGF; Oli-neu-cells; PC12-cells
Schlagwörter: Klf10; Klf11; Sp1-/Krüppelähnliche Transkriptionsfaktoren; Apoptose; Zellzyklusarrest; TGF-β; NGF; Oli-neu-Zellen; PC12-Zellen
 
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