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

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

doi:https://doi.org/10.1093/hmg/ddi316

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

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

Cardiology (AMC)

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

124 Citations (Scopus)

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

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 - 2005

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https://doi.org/10.1093/hmg/ddi316

Cite this

@article{840707d334e241c29fbe8149f5ecc264,

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-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",

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

year = "2005",

doi = "https://doi.org/10.1093/hmg/ddi316",

language = "English",

volume = "14",

pages = "2839--2849",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "19",

}

TY - JOUR

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

AU - van Berlo, J. H.

AU - Voncken, J. W.

AU - Kubben, N.

AU - Broers, J. L. V.

AU - Duisters, R.

AU - van Leeuwen, R. E. W.

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

AU - Ramaekers, F. C. S.

AU - Hutchison, C. J.

AU - Pinto, Y. M.

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-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

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-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

U2 - https://doi.org/10.1093/hmg/ddi316

DO - https://doi.org/10.1093/hmg/ddi316

M3 - Article

C2 - 16115815

SN - 0964-6906

VL - 14

SP - 2839

EP - 2849

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 19

ER -