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- Title
A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors.
- Authors
Van Berlo, J H; Voncken, J W; Kubben, N; Broers, J L V; Duisters, R; van Leeuwen, R E W; Crijns, H J G M; Ramaekers, F C S; Hutchison, C J; Pinto, Y M
- Abstract
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-beta1 (TGF-beta1) signalling impinges on the retinoblastoma protein (pRB) and SMADs, we tested the hypothesis that lamins modulate cellular responses to TGF-beta1 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-beta1. TGF-beta1 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-beta1 on collagen production, a marker of mesenchymal differentiation. Our findings implicate lamin A/C in control of gene activity downstream of TGF-beta1, via nuclear phosphatases such as PP2A. This biological function provides a novel explanation for the observed mesenchymal dysfunction in laminopathies.
- Publication
Human molecular genetics, 2005, Vol 14, Issue 19, p2839
- ISSN
0964-6906
- Publication type
Journal Article
- DOI
10.1093/hmg/ddi316