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[P31]: Involvement of ski in TGFbeta‐induced proliferation of Schwann cells
Author(s) -
Jacob C.,
Grabner H.,
Atanasoski S.,
Suter U.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.095
Subject(s) - citation , library science , citation impact , art history , art , computer science
TGFbeta induces proliferation or apoptosis of Schwann cells (the glia cells of the PNS), whereas it promotes growth inhibition and differentiation of epithelial cells. We aim to elucidate how these differences arise. One important player is the protooncogene Ski, a negative regulator of TGFbeta signaling that has been shown to play a key role in the control of Schwann cell proliferation and myelination. Ski can interact with different proteins, and we hypothesized that by doing so it can modulate the effects of TGFbeta. We studied TGFbeta signaling in Schwann cells and epithelial cells. Schwann cells are growth-arrested in defined medium containing growth factors (DM), and proliferate when TGFbeta is added, whereas epithelial cells proliferate in DM and differentiate upon TGFbeta treatment. In TGFbeta-treated Schwann cells, Ski and retinoblastoma protein (Rb) accumulated in the cytoplasm, where they colocalized, whereas this was not observed in epithelial cells. Schwann cells expressed 3-fold higher levels of Ski than did epithelial cells. TGFbeta strongly down-regulated Ski in epithelial cells but not in Schwann cells. Cytoplasmic colocalization was also seen in Ski-overexpressing Schwann cells, and the amount of Ski and Rb colocalized in the cytoplasm increased upon TGFbeta treatment. In DM, overexpressing cells proliferated more compared to cells expressing endogenous levels of Ski, but TGFbeta-induced proliferation was not increased. TGFbeta treatment of Ski-overexpressing epithelial cells led to Ski and Rb colocalization in the cytoplasm, inhibition of TGFbeta-induced differentiation, and promotion of TGFbetainduced proliferation. Our results suggest that the levels of Ski determine its interaction with Rb in the cytoplasm, and that this mechanism could mediate a part of TGFbeta-induced proliferation in Schwann cells. TGFbeta may thus induce the proliferation of Schwann cells by a Smad-dependent pathway inhibited by Ski, but also by a Ski/Rb-pathway regulated by Ski levels.