Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1.

CREB3L1 (cAMP response element binding protein 3-like 1), a transcription factor synthesized as a membrane-bound precursor and activated through Regulated Intramembrane Proteolysis (RIP), is essential for collagen production by osteoblasts during bone development. Here, we show that TGF-β (transform...

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Autores principales:	Qiuyue Chen, Ching-En Lee, Bray Denard, Jin Ye
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8adbf80cb35a400ebdc815c92ce9351f
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spelling	oai:doaj.org-article:8adbf80cb35a400ebdc815c92ce9351f2021-11-25T05:56:53ZSustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1.1932-620310.1371/journal.pone.0108528https://doaj.org/article/8adbf80cb35a400ebdc815c92ce9351f2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108528https://doaj.org/toc/1932-6203CREB3L1 (cAMP response element binding protein 3-like 1), a transcription factor synthesized as a membrane-bound precursor and activated through Regulated Intramembrane Proteolysis (RIP), is essential for collagen production by osteoblasts during bone development. Here, we show that TGF-β (transforming growth factor-β), a cytokine known to stimulate production of collagen during wound healing and fibrotic diseases, induces proteolytic activation of CREB3L1 in human A549 cells. This activation results from inhibition of expression of TM4SF20 (transmembrane 4 L6 family member 20), which normally inhibits RIP of CREB3L1. Cleavage of CREB3L1 releases its NH2-terminal domain from membranes, allowing it to enter the nucleus where it binds to Smad4 to activate transcription of genes encoding proteins required for assembly of collagen-containing extracellular matrix. Our findings raise the possibility that inhibition of RIP of CREB3L1 could prevent excess deposition of collagen in certain fibrotic diseases.Qiuyue ChenChing-En LeeBray DenardJin YePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e108528 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qiuyue Chen Ching-En Lee Bray Denard Jin Ye Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1.
description	CREB3L1 (cAMP response element binding protein 3-like 1), a transcription factor synthesized as a membrane-bound precursor and activated through Regulated Intramembrane Proteolysis (RIP), is essential for collagen production by osteoblasts during bone development. Here, we show that TGF-β (transforming growth factor-β), a cytokine known to stimulate production of collagen during wound healing and fibrotic diseases, induces proteolytic activation of CREB3L1 in human A549 cells. This activation results from inhibition of expression of TM4SF20 (transmembrane 4 L6 family member 20), which normally inhibits RIP of CREB3L1. Cleavage of CREB3L1 releases its NH2-terminal domain from membranes, allowing it to enter the nucleus where it binds to Smad4 to activate transcription of genes encoding proteins required for assembly of collagen-containing extracellular matrix. Our findings raise the possibility that inhibition of RIP of CREB3L1 could prevent excess deposition of collagen in certain fibrotic diseases.
format	article
author	Qiuyue Chen Ching-En Lee Bray Denard Jin Ye
author_facet	Qiuyue Chen Ching-En Lee Bray Denard Jin Ye
author_sort	Qiuyue Chen
title	Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1.
title_short	Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1.
title_full	Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1.
title_fullStr	Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1.
title_full_unstemmed	Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1.
title_sort	sustained induction of collagen synthesis by tgf-β requires regulated intramembrane proteolysis of creb3l1.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8adbf80cb35a400ebdc815c92ce9351f
work_keys_str_mv	AT qiuyuechen sustainedinductionofcollagensynthesisbytgfbrequiresregulatedintramembraneproteolysisofcreb3l1 AT chingenlee sustainedinductionofcollagensynthesisbytgfbrequiresregulatedintramembraneproteolysisofcreb3l1 AT braydenard sustainedinductionofcollagensynthesisbytgfbrequiresregulatedintramembraneproteolysisofcreb3l1 AT jinye sustainedinductionofcollagensynthesisbytgfbrequiresregulatedintramembraneproteolysisofcreb3l1
_version_	1718414353871405056

Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1.

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