A-type lamins are essential for TGF-β1 induced PP2A to dephosphorylate transcription factors | Zendy

Jop H. van Berlo | Zendy; Jan Willem Voncken | Zendy; Nard Kubben | Zendy; Jos L. V. Broers | Zendy; Rudy F. Duisters | Zendy; Rick E.W. van Leeuwen | Zendy; Harry J.G.M. Crijns | Zendy; Frans C. S. Ramaekers | Zendy; Christopher J. Hutchison | Zendy; Yigal M. Pinto | Zendy

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A-type lamins are essential for TGF-β1 induced PP2A to dephosphorylate transcription factors

Author(s) -

Jop H. van Berlo,

Jan Willem Voncken,

Nard Kubben,

Jos L. V. Broers,

Rudy F. Duisters,

Rick E.W. van Leeuwen,

Harry J.G.M. Crijns,

Frans C. S. Ramaekers,

Christopher J. Hutchison,

Yigal M. Pinto

Publication year - 2005

Publication title -

human molecular genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.811

H-Index - 276

eISSN - 1460-2083

pISSN - 0964-6906

DOI - 10.1093/hmg/ddi316

Subject(s) - lamin , biology , microbiology and biotechnology , transcription factor , transforming growth factor , protein phosphatase 2 , nuclear lamina , mesenchymal stem cell , transforming growth factor beta , phosphatase , cancer research , genetics , nuclear protein , gene , phosphorylation , nucleus

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.

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