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

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

doi:10.1093/hmg/ddi316

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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-beta 1 (TGF-beta 1) signalling impinges on the retinoblastoma protein (pRB) and SMADs, we tested the hypothesis that lamins modulate cellular responses to TGF-beta 1 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-beta 1. TGF-beta 1 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-beta 1 on collagen production, a marker of mesenchymal differentiation. Our findings implicate lamin A/C in control of gene activity downstream of TGF-beta 1, via nuclear phosphatases such as PP2A. This biological function provides a novel explanation for the observed mesenchymal dysfunction in laminopathies.

Original language	English
Pages (from-to)	2839-2849
Journal	Human Molecular Genetics
Volume	14
Issue number	19
DOIs	https://doi.org/10.1093/hmg/ddi316
Publication status	Published - 1 Jan 2005

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Van Berlo, J. H., Voncken, M. J. W. M., Kubben, N., Broers, J. L. V., Duisters, R. F. J. J., van Leeuwen, R. E., Crijns, H. J. G. M., Ramaekers, F. C. S., Hutchison, C. J., & Pinto, Y. M. (2005). A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors. Human Molecular Genetics, 14(19), 2839-2849. https://doi.org/10.1093/hmg/ddi316

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title = "A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors.",

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-beta 1 (TGF-beta 1) signalling impinges on the retinoblastoma protein (pRB) and SMADs, we tested the hypothesis that lamins modulate cellular responses to TGF-beta 1 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-beta 1. TGF-beta 1 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-beta 1 on collagen production, a marker of mesenchymal differentiation. Our findings implicate lamin A/C in control of gene activity downstream of TGF-beta 1, via nuclear phosphatases such as PP2A. This biological function provides a novel explanation for the observed mesenchymal dysfunction in laminopathies.",

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doi = "10.1093/hmg/ddi316",

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T1 - A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors.

AU - Van Berlo, J.H.

AU - Voncken, M.J.W.M.

AU - Kubben, N.

AU - Broers, J.L.V.

AU - Duisters, R.F.J.J.

AU - van Leeuwen, R.E.

AU - Crijns, H.J.G.M.

AU - Ramaekers, F.C.S.

AU - Hutchison, C.J.

AU - Pinto, Y.M.

PY - 2005/1/1

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N2 - 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-beta 1 (TGF-beta 1) signalling impinges on the retinoblastoma protein (pRB) and SMADs, we tested the hypothesis that lamins modulate cellular responses to TGF-beta 1 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-beta 1. TGF-beta 1 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-beta 1 on collagen production, a marker of mesenchymal differentiation. Our findings implicate lamin A/C in control of gene activity downstream of TGF-beta 1, via nuclear phosphatases such as PP2A. This biological function provides a novel explanation for the observed mesenchymal dysfunction in laminopathies.

AB - 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-beta 1 (TGF-beta 1) signalling impinges on the retinoblastoma protein (pRB) and SMADs, we tested the hypothesis that lamins modulate cellular responses to TGF-beta 1 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-beta 1. TGF-beta 1 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-beta 1 on collagen production, a marker of mesenchymal differentiation. Our findings implicate lamin A/C in control of gene activity downstream of TGF-beta 1, via nuclear phosphatases such as PP2A. This biological function provides a novel explanation for the observed mesenchymal dysfunction in laminopathies.

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DO - 10.1093/hmg/ddi316

M3 - Article

SN - 0964-6906

VL - 14

SP - 2839

EP - 2849

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 19

ER -

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

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