Premature senescence and increased TGFβ signaling in the absence of Tgif1.

Transforming growth factor β (TGFβ) signaling regulates cell cycle progression in several cell types, primarily by inducing a G1 cell cycle arrest. Tgif1 is a transcriptional corepressor that limits TGFβ responsive gene expression. Here we demonstrate that primary mouse embryo fibroblasts (MEFs) lac...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Brad J Zerlanko, Laurent Bartholin, Tiffany A Melhuish, David Wotton
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/847e1aa759ac47f39e947fdd1c4c2a7a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:847e1aa759ac47f39e947fdd1c4c2a7a
record_format	dspace
spelling	oai:doaj.org-article:847e1aa759ac47f39e947fdd1c4c2a7a2021-11-18T07:22:08ZPremature senescence and increased TGFβ signaling in the absence of Tgif1.1932-620310.1371/journal.pone.0035460https://doaj.org/article/847e1aa759ac47f39e947fdd1c4c2a7a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22514746/?tool=EBIhttps://doaj.org/toc/1932-6203Transforming growth factor β (TGFβ) signaling regulates cell cycle progression in several cell types, primarily by inducing a G1 cell cycle arrest. Tgif1 is a transcriptional corepressor that limits TGFβ responsive gene expression. Here we demonstrate that primary mouse embryo fibroblasts (MEFs) lacking Tgif1 proliferate slowly, accumulate increased levels of DNA damage, and senesce prematurely. We also provide evidence that the effects of loss of Tgif1 on proliferation and senescence are not limited to primary cells. The increased DNA damage in Tgif1 null MEFs can be partially reversed by culturing cells at physiological oxygen levels, and growth in normoxic conditions also partially rescues the proliferation defect, suggesting that in the absence of Tgif1 primary MEFs are less able to cope with elevated levels of oxidative stress. Additionally, we show that Tgif1 null MEFs are more sensitive to TGFβ-mediated growth inhibition, and that treatment with a TGFβ receptor kinase inhibitor increases proliferation of Tgif1 null MEFs. Conversely, persistent treatment of wild type cells with low levels of TGFβ slows proliferation and induces senescence, suggesting that TGFβ signaling also contributes to cellular senescence. We suggest that in the absence of Tgif1, a persistent increase in TGFβ responsive transcription and a reduced ability to deal with hyperoxic stress result in premature senescence in primary MEFs.Brad J ZerlankoLaurent BartholinTiffany A MelhuishDavid WottonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35460 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brad J Zerlanko Laurent Bartholin Tiffany A Melhuish David Wotton Premature senescence and increased TGFβ signaling in the absence of Tgif1.
description	Transforming growth factor β (TGFβ) signaling regulates cell cycle progression in several cell types, primarily by inducing a G1 cell cycle arrest. Tgif1 is a transcriptional corepressor that limits TGFβ responsive gene expression. Here we demonstrate that primary mouse embryo fibroblasts (MEFs) lacking Tgif1 proliferate slowly, accumulate increased levels of DNA damage, and senesce prematurely. We also provide evidence that the effects of loss of Tgif1 on proliferation and senescence are not limited to primary cells. The increased DNA damage in Tgif1 null MEFs can be partially reversed by culturing cells at physiological oxygen levels, and growth in normoxic conditions also partially rescues the proliferation defect, suggesting that in the absence of Tgif1 primary MEFs are less able to cope with elevated levels of oxidative stress. Additionally, we show that Tgif1 null MEFs are more sensitive to TGFβ-mediated growth inhibition, and that treatment with a TGFβ receptor kinase inhibitor increases proliferation of Tgif1 null MEFs. Conversely, persistent treatment of wild type cells with low levels of TGFβ slows proliferation and induces senescence, suggesting that TGFβ signaling also contributes to cellular senescence. We suggest that in the absence of Tgif1, a persistent increase in TGFβ responsive transcription and a reduced ability to deal with hyperoxic stress result in premature senescence in primary MEFs.
format	article
author	Brad J Zerlanko Laurent Bartholin Tiffany A Melhuish David Wotton
author_facet	Brad J Zerlanko Laurent Bartholin Tiffany A Melhuish David Wotton
author_sort	Brad J Zerlanko
title	Premature senescence and increased TGFβ signaling in the absence of Tgif1.
title_short	Premature senescence and increased TGFβ signaling in the absence of Tgif1.
title_full	Premature senescence and increased TGFβ signaling in the absence of Tgif1.
title_fullStr	Premature senescence and increased TGFβ signaling in the absence of Tgif1.
title_full_unstemmed	Premature senescence and increased TGFβ signaling in the absence of Tgif1.
title_sort	premature senescence and increased tgfβ signaling in the absence of tgif1.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/847e1aa759ac47f39e947fdd1c4c2a7a
work_keys_str_mv	AT bradjzerlanko prematuresenescenceandincreasedtgfbsignalingintheabsenceoftgif1 AT laurentbartholin prematuresenescenceandincreasedtgfbsignalingintheabsenceoftgif1 AT tiffanyamelhuish prematuresenescenceandincreasedtgfbsignalingintheabsenceoftgif1 AT davidwotton prematuresenescenceandincreasedtgfbsignalingintheabsenceoftgif1
_version_	1718423544076959744

Premature senescence and increased TGFβ signaling in the absence of Tgif1.

Ejemplares similares