A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors

J.H. Berlo, van, J.W. Voncken, N. Kubben, J.L.V. Broers, R. Duisters, R.E.W. Leeuwen, van, H.J.G.M. Crijns, F.C.S. Ramaekers, C.J. Hutchison, Y. Pinto

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Diseases caused by mutations in lamins A and C (laminopathies) suggest a crucial role for A-type lamins in different cellular processes. Laminopathies mostly affect tissues of mesenchymal origin. As transforming growth factor-ß1 (TGF-ß1) signalling impinges on the retinoblastoma protein (pRB) and SMADs, we tested the hypothesis that lamins modulate cellular responses to TGF-ß1 signalling, via the regulation of these transcription factors in mesenchymal cells. Here, we report that A-type lamins are essential for the inhibition of fibroblast proliferation by TGF-ß1. TGF-ß1 dephosphorylated pRB through PP2A, both of which, we show, are associated with lamin A/C. In addition, lamin A/C modulates the effect of TGF-ß1 on collagen production, a marker of mesenchymal differentiation. Our findings implicate lamin A/C in control of gene activity downstream of TGF-ß1, via nuclear phosphatases such as PP2A. This biological function provides a novel explanation for the observed mesenchymal dysfunction in laminopathies.
Original languageEnglish
Pages (from-to)2839-49
JournalHuman Molecular Genetics
Issue number19
Publication statusPublished - 2005


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