KLF14-mediated TGFBRII silencing

Model of KLF14-mediated TGFβRII silencing. Activation of the TGFβRII would occur via TGFβ1 ligand initiating an up-regulation of the TGFβRII promoter by Sp1. In our model, activation of the TGFβ pathway also causes an induction of KLF14 expression (A), which would, in turn, bind to the TGFβRII promoter through its GC-rich sites (B), competing away Sp1 (C), recruiting the Sin3a/HDAC complex (D), and remodeling chromatin from a transcriptionally “active,” acetylated state to an “inactive” state with silencing methyl marks (E). Thus, KLF14 mediates a negative feedback loop to down-regulate the type II TGFβ receptor upon TGFβ stimulation.

Publication

Silencing of the Transforming Growth Factor-β (TGFβ) Receptor II by Krüppel-like Factor 14 Underscores the Importance of a Negative Feedback Mechanism in TGFβ Signaling. (2009) Mark J. Truty, et al. J Biol Chem. 2009 Mar 6;284(10):6291-6300. Figure: F7. All organisms Oryctolagus cuniculus Bos taurus Homo sapiens Drosophila melanogaster

Disease mentions