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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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-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
Volume14
Issue number19
DOIs
Publication statusPublished - 2005

Fingerprint

Lamin Type A
Transforming Growth Factor beta1
Transforming Growth Factors
Transcription Factors
Lamins
Retinoblastoma Protein
Differentiation Antigens
Phosphoric Monoester Hydrolases
Collagen
Fibroblasts
Mutation
Genes

Cite this

Berlo, van, J. H., Voncken, J. W., Kubben, N., Broers, J. L. V., Duisters, R., Leeuwen, van, R. E. W., ... Pinto, Y. (2005). A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors. Human Molecular Genetics, 14(19), 2839-49. https://doi.org/10.1093/hmg/ddi316
Berlo, van, J.H. ; Voncken, J.W. ; Kubben, N. ; Broers, J.L.V. ; Duisters, R. ; Leeuwen, van, R.E.W. ; Crijns, H.J.G.M. ; Ramaekers, F.C.S. ; Hutchison, C.J. ; Pinto, Y. / A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors. In: Human Molecular Genetics. 2005 ; Vol. 14, No. 19. pp. 2839-49.
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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-{\ss}1 (TGF-{\ss}1) signalling impinges on the retinoblastoma protein (pRB) and SMADs, we tested the hypothesis that lamins modulate cellular responses to TGF-{\ss}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-{\ss}1. TGF-{\ss}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-{\ss}1 on collagen production, a marker of mesenchymal differentiation. Our findings implicate lamin A/C in control of gene activity downstream of TGF-{\ss}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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Berlo, van, JH, Voncken, JW, Kubben, N, Broers, JLV, Duisters, R, Leeuwen, van, REW, Crijns, HJGM, Ramaekers, FCS, Hutchison, CJ & Pinto, Y 2005, 'A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors', Human Molecular Genetics, vol. 14, no. 19, pp. 2839-49. https://doi.org/10.1093/hmg/ddi316

A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors. / Berlo, van, J.H.; Voncken, J.W.; Kubben, N.; Broers, J.L.V.; Duisters, R.; Leeuwen, van, R.E.W.; Crijns, H.J.G.M.; Ramaekers, F.C.S.; Hutchison, C.J.; Pinto, Y.

In: Human Molecular Genetics, Vol. 14, No. 19, 2005, p. 2839-49.

Research output: Contribution to journalArticleAcademicpeer-review

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

AU - Berlo, van, J.H.

AU - Voncken, J.W.

AU - Kubben, N.

AU - Broers, J.L.V.

AU - Duisters, R.

AU - Leeuwen, van, R.E.W.

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

AU - Ramaekers, F.C.S.

AU - Hutchison, C.J.

AU - Pinto, Y.

PY - 2005

Y1 - 2005

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-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.

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-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.

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DO - 10.1093/hmg/ddi316

M3 - Article

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VL - 14

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JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

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ER -

Berlo, van JH, Voncken JW, Kubben N, Broers JLV, Duisters R, Leeuwen, van REW et al. A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors. Human Molecular Genetics. 2005;14(19):2839-49. https://doi.org/10.1093/hmg/ddi316