A role of TGFß1 dependent 14-3-3σ phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance.

Transforming growth factor-β (TGFβ) is a potent regulator of tumorigenesis, although mechanisms defining its tumor suppressing and tumor promoting activities are not understood. Here we describe phosphoproteome profiling of TGFβ signaling in mammary epithelial cells, and show that 60 identified TGFβ...

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Autores principales:	Olena Zakharchenko, Monica Cojoc, Anna Dubrovska, Serhiy Souchelnytskyi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7e3baf0052944d389e90e6ba14ab7539
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spelling	oai:doaj.org-article:7e3baf0052944d389e90e6ba14ab75392021-11-18T07:43:25ZA role of TGFß1 dependent 14-3-3σ phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance.1932-620310.1371/journal.pone.0065163https://doaj.org/article/7e3baf0052944d389e90e6ba14ab75392013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23741479/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Transforming growth factor-β (TGFβ) is a potent regulator of tumorigenesis, although mechanisms defining its tumor suppressing and tumor promoting activities are not understood. Here we describe phosphoproteome profiling of TGFβ signaling in mammary epithelial cells, and show that 60 identified TGFβ-regulated phosphoproteins form a network with scale-free characteristics. The network highlighted interactions, which may distribute signaling inputs to regulation of cell proliferation, metabolism, differentiation and cell organization. In this report, we identified two novel and TGFβ-dependent phosphorylation sites of 14-3-3σ, i.e. Ser69 and Ser74. We observed that 14-3-3σ phosphorylation is a feed-forward mechanism in TGFβ/Smad3-dependent transcription. TGFβ-dependent 14-3-3σ phosphorylation may provide a scaffold for the formation of the protein complexes which include Smad3 and p53 at the Smad3-specific CAGA element. Furthermore, breast tumor xenograft studies in mice and radiobiological assays showed that phosphorylation of 14-3-3σ at Ser69 and Ser74 is involved in regulation of cancer progenitor population and radioresistance in breast cancer MCF7 cells. Our data suggest that TGFβ-dependent phosphorylation of 14-3-3σ orchestrates a functional interaction of TGFβ/Smad3 with p53, plays a role in the maintenance of cancer stem cells and could provide a new potential target for intervention in breast cancer.Olena ZakharchenkoMonica CojocAnna DubrovskaSerhiy SouchelnytskyiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e65163 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Olena Zakharchenko Monica Cojoc Anna Dubrovska Serhiy Souchelnytskyi A role of TGFß1 dependent 14-3-3σ phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance.
description	Transforming growth factor-β (TGFβ) is a potent regulator of tumorigenesis, although mechanisms defining its tumor suppressing and tumor promoting activities are not understood. Here we describe phosphoproteome profiling of TGFβ signaling in mammary epithelial cells, and show that 60 identified TGFβ-regulated phosphoproteins form a network with scale-free characteristics. The network highlighted interactions, which may distribute signaling inputs to regulation of cell proliferation, metabolism, differentiation and cell organization. In this report, we identified two novel and TGFβ-dependent phosphorylation sites of 14-3-3σ, i.e. Ser69 and Ser74. We observed that 14-3-3σ phosphorylation is a feed-forward mechanism in TGFβ/Smad3-dependent transcription. TGFβ-dependent 14-3-3σ phosphorylation may provide a scaffold for the formation of the protein complexes which include Smad3 and p53 at the Smad3-specific CAGA element. Furthermore, breast tumor xenograft studies in mice and radiobiological assays showed that phosphorylation of 14-3-3σ at Ser69 and Ser74 is involved in regulation of cancer progenitor population and radioresistance in breast cancer MCF7 cells. Our data suggest that TGFβ-dependent phosphorylation of 14-3-3σ orchestrates a functional interaction of TGFβ/Smad3 with p53, plays a role in the maintenance of cancer stem cells and could provide a new potential target for intervention in breast cancer.
format	article
author	Olena Zakharchenko Monica Cojoc Anna Dubrovska Serhiy Souchelnytskyi
author_facet	Olena Zakharchenko Monica Cojoc Anna Dubrovska Serhiy Souchelnytskyi
author_sort	Olena Zakharchenko
title	A role of TGFß1 dependent 14-3-3σ phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance.
title_short	A role of TGFß1 dependent 14-3-3σ phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance.
title_full	A role of TGFß1 dependent 14-3-3σ phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance.
title_fullStr	A role of TGFß1 dependent 14-3-3σ phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance.
title_full_unstemmed	A role of TGFß1 dependent 14-3-3σ phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance.
title_sort	role of tgfß1 dependent 14-3-3σ phosphorylation at ser69 and ser74 in the regulation of gene transcription, stemness and radioresistance.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7e3baf0052944d389e90e6ba14ab7539
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A role of TGFß1 dependent 14-3-3σ phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance.

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