Transcriptional regulation of the transforming growth factor-β2 promoter by cAMP-responsive element-binding protein (CREB) and activating transcription factor-1 (ATF-1) is modulated by protein kinases and the coactivators p300 and CREB-binding protein

Michelle L. Kingsley-Kallesen, David Lee Kelly, A Angie Rizzino

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Transcription of the transforming growth factor-β2 (TGF-β2) gene is dependent on a cAMP-response element/activating transcription factor (CRE/ATF) site that is bound by CREB and ATF-1 as well as an E-box motif that is bound by upstream stimulatory factors 1 and 2 (USF1 and USF2). To identify additional factors involved in the expression of the TGF-β2 gene, we employed F9 embryonal carcinoma (EC) cells, which express TGF-β2 only after the cells differentiate. We show that overexpression of the transcription factors, CREB, ATF-1, USF1, and USF2 dramatically increases TGF-β2 promoter activity in F9-differentiated cells. We further show that the coactivators p300 and CBP up-regulate the TGF-β2 promoter when CREB and ATF-1 are expressed in conjunction with protein kinases that phosphorylate CREB on serine 133 and ATF-1 on serine 63. Importantly, we identify the presence of serine 133-phosphorylated CREB in the nucleus of F9-differentiated cells but not in the nucleus of F9 EC cells. This phosphorylated form is present in whole cell extracts of both the parental and differentiated cells, suggesting that nuclear accumulation of serine 133-phosphorylated CREB is regulated during differentiation of F9 EC cells and is likely to play an important role in the activation of the TGF-β2 gene.

Original languageEnglish (US)
Pages (from-to)34020-34028
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number48
DOIs
StatePublished - Nov 26 1999

Fingerprint

Activating Transcription Factor 1
Transforming Growth Factors
Protein Binding
Protein Kinases
Carrier Proteins
Embryonal Carcinoma Stem Cells
Serine
Genes
p300-CBP Transcription Factors
Upstream Stimulatory Factors
Activating Transcription Factors
E-Box Elements
Response Elements
Transcription
Cell Extracts
Transcription Factors
Up-Regulation
Chemical activation
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{7edba4a6052f4bf5aa7d32196588f831,
title = "Transcriptional regulation of the transforming growth factor-β2 promoter by cAMP-responsive element-binding protein (CREB) and activating transcription factor-1 (ATF-1) is modulated by protein kinases and the coactivators p300 and CREB-binding protein",
abstract = "Transcription of the transforming growth factor-β2 (TGF-β2) gene is dependent on a cAMP-response element/activating transcription factor (CRE/ATF) site that is bound by CREB and ATF-1 as well as an E-box motif that is bound by upstream stimulatory factors 1 and 2 (USF1 and USF2). To identify additional factors involved in the expression of the TGF-β2 gene, we employed F9 embryonal carcinoma (EC) cells, which express TGF-β2 only after the cells differentiate. We show that overexpression of the transcription factors, CREB, ATF-1, USF1, and USF2 dramatically increases TGF-β2 promoter activity in F9-differentiated cells. We further show that the coactivators p300 and CBP up-regulate the TGF-β2 promoter when CREB and ATF-1 are expressed in conjunction with protein kinases that phosphorylate CREB on serine 133 and ATF-1 on serine 63. Importantly, we identify the presence of serine 133-phosphorylated CREB in the nucleus of F9-differentiated cells but not in the nucleus of F9 EC cells. This phosphorylated form is present in whole cell extracts of both the parental and differentiated cells, suggesting that nuclear accumulation of serine 133-phosphorylated CREB is regulated during differentiation of F9 EC cells and is likely to play an important role in the activation of the TGF-β2 gene.",
author = "Kingsley-Kallesen, {Michelle L.} and Kelly, {David Lee} and Rizzino, {A Angie}",
year = "1999",
month = "11",
day = "26",
doi = "10.1074/jbc.274.48.34020",
language = "English (US)",
volume = "274",
pages = "34020--34028",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "48",

}

TY - JOUR

T1 - Transcriptional regulation of the transforming growth factor-β2 promoter by cAMP-responsive element-binding protein (CREB) and activating transcription factor-1 (ATF-1) is modulated by protein kinases and the coactivators p300 and CREB-binding protein

AU - Kingsley-Kallesen, Michelle L.

AU - Kelly, David Lee

AU - Rizzino, A Angie

PY - 1999/11/26

Y1 - 1999/11/26

N2 - Transcription of the transforming growth factor-β2 (TGF-β2) gene is dependent on a cAMP-response element/activating transcription factor (CRE/ATF) site that is bound by CREB and ATF-1 as well as an E-box motif that is bound by upstream stimulatory factors 1 and 2 (USF1 and USF2). To identify additional factors involved in the expression of the TGF-β2 gene, we employed F9 embryonal carcinoma (EC) cells, which express TGF-β2 only after the cells differentiate. We show that overexpression of the transcription factors, CREB, ATF-1, USF1, and USF2 dramatically increases TGF-β2 promoter activity in F9-differentiated cells. We further show that the coactivators p300 and CBP up-regulate the TGF-β2 promoter when CREB and ATF-1 are expressed in conjunction with protein kinases that phosphorylate CREB on serine 133 and ATF-1 on serine 63. Importantly, we identify the presence of serine 133-phosphorylated CREB in the nucleus of F9-differentiated cells but not in the nucleus of F9 EC cells. This phosphorylated form is present in whole cell extracts of both the parental and differentiated cells, suggesting that nuclear accumulation of serine 133-phosphorylated CREB is regulated during differentiation of F9 EC cells and is likely to play an important role in the activation of the TGF-β2 gene.

AB - Transcription of the transforming growth factor-β2 (TGF-β2) gene is dependent on a cAMP-response element/activating transcription factor (CRE/ATF) site that is bound by CREB and ATF-1 as well as an E-box motif that is bound by upstream stimulatory factors 1 and 2 (USF1 and USF2). To identify additional factors involved in the expression of the TGF-β2 gene, we employed F9 embryonal carcinoma (EC) cells, which express TGF-β2 only after the cells differentiate. We show that overexpression of the transcription factors, CREB, ATF-1, USF1, and USF2 dramatically increases TGF-β2 promoter activity in F9-differentiated cells. We further show that the coactivators p300 and CBP up-regulate the TGF-β2 promoter when CREB and ATF-1 are expressed in conjunction with protein kinases that phosphorylate CREB on serine 133 and ATF-1 on serine 63. Importantly, we identify the presence of serine 133-phosphorylated CREB in the nucleus of F9-differentiated cells but not in the nucleus of F9 EC cells. This phosphorylated form is present in whole cell extracts of both the parental and differentiated cells, suggesting that nuclear accumulation of serine 133-phosphorylated CREB is regulated during differentiation of F9 EC cells and is likely to play an important role in the activation of the TGF-β2 gene.

UR - http://www.scopus.com/inward/record.url?scp=0033607535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033607535&partnerID=8YFLogxK

U2 - 10.1074/jbc.274.48.34020

DO - 10.1074/jbc.274.48.34020

M3 - Article

VL - 274

SP - 34020

EP - 34028

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 48

ER -