Identification of human myometrial target genes of the cAMP pathway: the role of cAMP-response element binding (CREB) and modulator (CREMalpha and CREMtau2alpha) proteins
- PMID: 15691874
- DOI: 10.1677/jme.1.01594
Identification of human myometrial target genes of the cAMP pathway: the role of cAMP-response element binding (CREB) and modulator (CREMalpha and CREMtau2alpha) proteins
Abstract
cAMP-response element (CRE) binding (CREB) and modulator (CREM) proteins, activated by protein kinase A-mediated phosphorylation, bind as homo- and heterodimers to promoters containing CRE and activator protein 1 (AP-1) sites to alter target-gene expression. We have previously reported differential expression of CREB and CREM splice variants CREMalpha and CREMtau2alpha in human myometrium during pregnancy and labour. Via microarray studies with cultured myometrial cells stably transfected with CREB, CREMalpha and CREMtau2alpha cDNAs, CREB affected the expression of 958 genes; 522 being up-regulated and 436 down-regulated. CREMalpha altered the expression of 118 genes; 71 were increased and 47 decreased. CREMtau2alpha affected 220 genes; 148 were activated and 72 repressed. Notably, genes affected by CREB, CREMalpha and CREMtau2alpha belong to largely discrete groups: less than 9% were affected by more than one factor. Genes involved in regulation of cell death and apoptosis, growth and maintenance, signal transduction, physiological and developmental processes, protein kinase cascades, extracellular matrix, cytoskeleton, cell-cycle regulation, transport, and a variety of enzymes, intracellular components and nucleic acid-binding proteins have been described, many of which are involved in the modulation of myometrial activity during pregnancy and parturition.
Similar articles
-
Identification of human myometrial target genes of the c-Jun NH2-terminal kinase (JNK) pathway: the role of activating transcription factor 2 (ATF2) and a novel spliced isoform ATF2-small.J Mol Endocrinol. 2005 Feb;34(1):19-35. doi: 10.1677/jme.1.01608. J Mol Endocrinol. 2005. PMID: 15691875
-
CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes.Oncogene. 1999 Feb 25;18(8):1569-79. doi: 10.1038/sj.onc.1202463. Oncogene. 1999. PMID: 10102627
-
Loss of expression of the ubiquitous transcription factor cAMP response element-binding protein (CREB) and compensatory overexpression of the activator CREMtau in the human adrenocortical cancer cell line H295R.J Clin Endocrinol Metab. 2000 Jan;85(1):345-54. doi: 10.1210/jcem.85.1.6307. J Clin Endocrinol Metab. 2000. PMID: 10634409
-
Coupling cAMP signaling to transcription in the liver: pivotal role of CREB and CREM.Exp Cell Res. 2002 May 1;275(2):143-54. doi: 10.1006/excr.2002.5491. Exp Cell Res. 2002. PMID: 11969286 Review.
-
Coupling transcription to signaling pathways: cAMP and nuclear factor cAMP-responsive element modulator.Adv Second Messenger Phosphoprotein Res. 1997;31:63-74. Adv Second Messenger Phosphoprotein Res. 1997. PMID: 9344242 Review. No abstract available.
Cited by
-
Disruption of β-Catenin-Dependent Wnt Signaling in Colon Cancer Cells Remodels the Microenvironment to Promote Tumor Invasion.Mol Cancer Res. 2022 Mar 1;20(3):468-484. doi: 10.1158/1541-7786.MCR-21-0349. Mol Cancer Res. 2022. PMID: 34799404 Free PMC article.
-
cAMP-responsive element modulator (CREM)α protein induces interleukin 17A expression and mediates epigenetic alterations at the interleukin-17A gene locus in patients with systemic lupus erythematosus.J Biol Chem. 2011 Dec 16;286(50):43437-46. doi: 10.1074/jbc.M111.299313. Epub 2011 Oct 24. J Biol Chem. 2011. PMID: 22025620 Free PMC article.
-
cAMP-responsive element modulator α (CREMα) suppresses IL-17F protein expression in T lymphocytes from patients with systemic lupus erythematosus (SLE).J Biol Chem. 2012 Feb 10;287(7):4715-25. doi: 10.1074/jbc.M111.323261. Epub 2011 Dec 19. J Biol Chem. 2012. PMID: 22184122 Free PMC article. Clinical Trial.
-
cAMP-responsive element modulator (CREM)α protein signaling mediates epigenetic remodeling of the human interleukin-2 gene: implications in systemic lupus erythematosus.J Biol Chem. 2011 Dec 16;286(50):43429-36. doi: 10.1074/jbc.M111.299339. Epub 2011 Oct 5. J Biol Chem. 2011. PMID: 21976679 Free PMC article.
-
cAMP-responsive element modulator α (CREMα) contributes to decreased Notch-1 expression in T cells from patients with active systemic lupus erythematosus (SLE).J Biol Chem. 2012 Dec 14;287(51):42525-32. doi: 10.1074/jbc.M112.425371. Epub 2012 Nov 2. J Biol Chem. 2012. PMID: 23124208 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials