Atorvastatin prevents carbohydrate response element binding protein activation in the fructose-fed rat by activating protein kinase A

Hepatology ◽  
2008 ◽  
Vol 49 (1) ◽  
pp. 106-115 ◽  
Author(s):  
Ricardo Rodríguez-Calvo ◽  
Emma Barroso ◽  
Lucía Serrano ◽  
Teresa Coll ◽  
Rosa M. Sánchez ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Binding Protein ◽  
Response Element ◽  
Protein Activation ◽  
Element Binding Protein ◽  
Kinase A

scholarly journals Combinatorial Roles of Protein Kinase A, Ets2, and 3′,5′-Cyclic-Adenosine Monophosphate Response Element-Binding Protein-Binding Protein/p300 in the Transcriptional Control of Interferon-τ Expression in a Trophoblast Cell Line

2008 ◽  
Vol 22 (2) ◽  
pp. 331-343 ◽  
Author(s):  
Padmalaya Das ◽  
Toshihiko Ezashi ◽  
Rangan Gupta ◽  
R. Michael Roberts
Keyword(s):  
Protein Kinase ◽  
Protein Binding ◽  
Binding Site ◽  
Protein Kinase A ◽  
Binding Protein ◽  
Proximal Promoter ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein ◽  
Kinase A

Abstract In ruminants, conceptus interferon-τ (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.

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