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

Qiuyue Chen, Ching En Lee, Bray Denard, Jin Ye

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere108528
JournalPLoS One
Volume9
Issue number10
DOIs
StatePublished - Oct 13 2014

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Proteolysis
Cyclic AMP Response Element-Binding Protein
transforming growth factors
response elements
Transforming Growth Factors
proteolysis
collagen
binding proteins
Collagen
synthesis
Chemical activation
Membranes
Enzyme inhibition
Gene encoding
skeletal development
osteoblasts
Bone Development
Osteoblasts
Transcription
tissue repair

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1. / Chen, Qiuyue; Lee, Ching En; Denard, Bray; Ye, Jin.

In: PLoS One, Vol. 9, No. 10, e108528, 13.10.2014.

Research output: Contribution to journalArticle

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