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Identification of human myometrial target genes of the cAMP pathway: The role of cAMP-response element binding (CREB) and modulator (CREMα and CREMτ2α) proteins

Lookup NU author(s): Dr Jarrod Bailey, Dr Alison Tyson-Capper, Kate Gilmore, Professor Stephen Robson, Professor Nick Europe-Finner

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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 CREMα and CREMτ2α in human myometrium during pregnancy and labour. Via microarray studies with cultured myometrial cells stably transfected with CREB, CREMα and CREMτ2α cDNAs, CREB affected the expression of 958 genes; 522 being up-regulated and 436 down-regulated. CREMα altered the expression of 118 genes; 71 were increased and 47 decreased. CREMτ2α affected 220 genes; 148 were activated and 72 repressed. Notably, genes affected by CREB, CREMα and CREMτ2α 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. © 2005 Society for Endocrinology.


Publication metadata

Author(s): Bailey J, Tyson-Capper AJ, Gilmore K, Robson SC, Europe-Finner GN

Publication type: Article

Publication status: Published

Journal: Journal of Molecular Endocrinology

Year: 2005

Volume: 34

Issue: 1

Pages: 1-17

Print publication date: 01/02/2005

ISSN (print): 0952-5041

ISSN (electronic): 1479-6813

Publisher: Society for Endocrinology.

URL: http://dx.doi.org/10.1677/jme.1.01594

DOI: 10.1677/jme.1.01594

PubMed id: 15691874


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