This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bailey, J. Articles by Europe-Finner, G. N. Search for Related Content PubMed PubMed Citation Articles by Bailey, J. Articles by Europe-Finner, G. N.

Characterization and Functional Analysis of cAMP Response Element Modulator Protein and Activating Transcription Factor 2 (ATF2) Isoforms in the Human Myometrium during Pregnancy and Labor: Identification of a Novel ATF2 Species with Potent Transactivation Properties

Department of Obstetrics and Gynaecology, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, United Kingdom

Address all correspondence and requests for reprints to: Dr. Jarrod Bailey, Department of Obstetrics and Gynaecology, University of Newcastle upon Tyne, Royal Victoria Infirmary, Fourth Floor Leazes Wing, Newcastle upon Tyne NE1 4LP, United Kingdom. E-mail: ; or . g.n.europe-finner{at}ncl.ac.uk

Abstract

There is now extensive evidence to indicate that components of the cAMP signaling pathway are up-regulated in the human myometrium during pregnancy so as to potentiate the maintenance of uterine quiescence until term. In many tissue and cell types, increased signaling of the cAMP pathway results in profound changes in gene expression that are catalyzed via stimulation of PKA and activation of cAMP-dependent transcription factors that bind cAMP response elements (CREs) within the promoter regions of affected genes. In the myometrium, these CRE containing genes include ß2-adrenoceptor, cyclo-oxygenase 2, oxytocin receptor, and connexin-43. In preliminary investigations, we reported the differential expression of members of the cAMP bZIP protein family in the myometrium during pregnancy and labor. In this present study, we have now identified and functionally characterized these proteins with respect to myometrial gene expression. We report the identification of a 39,000 mol wt CRE response element modulator protein (CREM)2 protein having both transactivation and transrepressor properties whose expression is sequentially decreased in the myometrium during gestation and parturition. In contrast, expression of a myometrial 28,000 mol wt CREM protein having only transrepressor actions progressively increased in the myometrium during pregnancy and labor. Similarly, we have isolated two ATF2 proteins of 60,000 and 28,000 mol wts, which represent full-length ATF2 and a novel small isoform of ATF2 that we have termed ATF2-small (ATF2-sm). These proteins are potent transactivators of gene expression and appear to be spatially expressed within the myometrium of the upper and lower uterine regions. The identification and functional characterization of these basic region/leucine zipper proteins in the myometrium may provide further insight into the molecular mechanisms regulating uterine activity during fetal maturation and parturition.

This article has been cited by other articles:

				N. R. Chapman, I. Smyrnias, D. O. C. Anumba, G. N. Europe-Finner, and S. C. Robson Expression of the GTP-Binding Protein (G{alpha}s) Is Repressed by the Nuclear Factor {kappa}B RelA Subunit in Human Myometrium Endocrinology, November 1, 2005; 146(11): 4994 - 5002. [Abstract] [Full Text] [PDF]

				A. J. Tyson-Capper, J. Bailey, A. R. Krainer, S. C. Robson, and G. N. Europe-Finner The Switch in Alternative Splicing of Cyclic AMP-response Element Modulator Protein CREM{tau}2{alpha} (Activator) to CREM{alpha} (Repressor) in Human Myometrial Cells Is Mediated by SRp40 J. Biol. Chem., October 14, 2005; 280(41): 34521 - 34529. [Abstract] [Full Text] [PDF]

				H. A. Otun, M. W.J. MacDougall, J. Bailey, G. N. Europe-Finner, and S. C. Robson Spatial and Temporal Expression of the Myometrial Mitogen-Activated Protein Kinases p38 and ERK1/2 in the Human Uterus During Pregnancy and Labor Reproductive Sciences, April 1, 2005; 12(3): 185 - 190. [Abstract] [PDF]

				J. Bailey, A. J Tyson-Capper, K. Gilmore, S. C Robson, and G N. Europe-Finner Identification of human myometrial target genes of the cAMP pathway: the role of cAMP-response element binding (CREB) and modulator (CREM{alpha} and CREM{tau}2{alpha}) proteins J. Mol. Endocrinol., February 1, 2005; 34(1): 1 - 17. [Abstract] [Full Text] [PDF]

				J. Bailey and G N. Europe-Finner 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., February 1, 2005; 34(1): 19 - 35. [Abstract] [Full Text] [PDF]

				J. Yao, N. Hiramatsu, Y. Zhu, T. Morioka, M. Takeda, T. Oite, and M. Kitamura Nitric Oxide-Mediated Regulation of Connexin43 Expression and Gap Junctional Intercellular Communication in Mesangial Cells J. Am. Soc. Nephrol., January 1, 2005; 16(1): 58 - 67. [Abstract] [Full Text] [PDF]

				E. I. Azzam, S. M. de Toledo, and J. B. Little Expression of CONNEXIN43 Is Highly Sensitive to Ionizing Radiation and Other Environmental Stresses Cancer Res., November 1, 2003; 63(21): 7128 - 7135. [Abstract] [Full Text] [PDF]

				J. C. SAEZ, V. M. BERTHOUD, M. C. BRANES, A. D. MARTINEZ, and E. C. BEYER Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions Physiol Rev, October 1, 2003; 83(4): 1359 - 1400. [Abstract] [Full Text] [PDF]