Combinatorial Roles of Protein Kinase A, Ets2 and CBP/p300 in the Transcriptional Control of Interferon-tau Expression in a Trophoblast Cell Line

MOspace/Manakin Repository

Breadcrumbs Navigation

Combinatorial Roles of Protein Kinase A, Ets2 and CBP/p300 in the Transcriptional Control of Interferon-tau Expression in a Trophoblast Cell Line

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/8764

[+] show full item record


Title: Combinatorial Roles of Protein Kinase A, Ets2 and CBP/p300 in the Transcriptional Control of Interferon-tau Expression in a Trophoblast Cell Line
Author: Das, Padmalaya, 1972-; Ezashi, Toshihiko; Gupta, Rangan, 1978-; Roberts, R. M. (Robert Michael), 1940-
Keywords: synergism
transfection
trophectoderm
maternal responses
Date: 2008-02
Publisher: Molecular Endocrinology
Citation: Molecular Endocrinology, 22(2), 331-343, 2008.
Abstract: In ruminants, conceptus interferon-tau (IFNT) production is necessary for maintenance of pregnancy. We examined the role of protein kinase A (PKA) in regulating IFNT expression through the activation of Ets2 in JAr choriocarcinoma cells. Although overexpression of the catalytic subunit of PKA or the addition of 8-bromo-cAMP had little ability to up-regulate boIFNT1 reporter constructs on their own, coexpression with Ets2 led to a large increase in gene expression. Progressive truncation of reporter constructs indicated that the site of PKA/Ets2 responsiveness lay in a region of the promoter between -126 and -67, which lacks a cAMP response element but contains the functional Ets2-binding site and an activator protein 1 (AP1) site. Specific mutation of the former reduced the PKA/Ets2 effects by more than 98%, whereas mutation of an AP1-binding site adjacent to the Ets2 site or pharmacological inhibition of MAPK kinase 2 led to a doubling of the combined Ets2/PKA effects, suggesting there is antagonism between the Ras/MAPK pathway and the PKA signal transduction pathway. Although Ets2 is not a substrate for PKA, lowering the effective concentrations of the coactivators, cAMP response element-binding protein-binding protein (CBP)/p300, known PKA targets, reduced the ability of PKA to synergize with Ets2, suggesting that PKA effects on IFNT regulation might be mediated through CBP/p300 coactivation, particularly as CBP and Ets2 occupy the proximal promoter region of IFNT in bovine trophoblast CT-1 cells. The up-regulation of IFNT in the elongating bovine conceptus is likely due to the combinatorial effects of PKA, Ets2, and CBP/p300 and triggered via growth factors released from maternal endometrium.
URI: http://hdl.handle.net/10355/8764

This item appears in the following Collection(s)

[+] show full item record