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Expression and localization of Ski determine cell type–specific TGFβ signaling effects on the cell cycle

¹ Department of Biology, Institute of Cell Biology, ETH Zurich, CH-8093 Zurich, Switzerland
² Department of Biomedicine, Institute of Physiology, University of Basel, CH-4056 Basel, Switzerland

Correspondence to Claire Jacob: claire.jacob{at}cell.biol.ethz.ch

Transforming growth factor β (TGFβ) promotes epithelial cell differentiation but induces Schwann cell proliferation. We show that the protooncogene Ski (Sloan-Kettering viral oncogene homologue) is an important regulator of these effects. TGFβ down-regulates Ski in epithelial cells but not in Schwann cells. In Schwann cells but not in epithelial cells, retinoblastoma protein (Rb) is up-regulated by TGFβ. Additionally, both Ski and Rb move to the cytoplasm, where they partially colocalize. In vivo, Ski and phospho-Rb (pRb) appear to interact in the Schwann cell cytoplasm of developing sciatic nerves. Ski overexpression induces Rb hyperphosphorylation, proliferation, and colocalization of both proteins in Schwann cell and epithelial cell cytoplasms independently of TGFβ treatment. Conversely, Ski knockdown in Schwann cells blocks TGFβ-induced proliferation and pRb cytoplasmic relocalization. Our findings reveal a critical function of fine-tuned Ski levels in the control of TGFβ effects on the cell cycle and suggest that at least a part of Ski regulatory effects on TGFβ-induced proliferation of Schwann cells is caused by its concerted action with Rb.

Abbreviations used in this paper: dbcAMP, dibutyryl cAMP; DM, defined medium; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PMP22, peripheral myelin protein 22; pRb, phospho-Rb; Rb, retinoblastoma protein; RIPA, radioimmunoprecipitation assay; shRNA, short hairpin RNA; SMA, smooth muscle actin.

© 2008 Jacob et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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