Differential regulation and transcriptional control of immediate early gene expression in forskolin-treated WEHI7.2 thymoma cells

Molecular Endocrinology
D MaoD R Dowd

Abstract

Agents that increase intracellular cAMP are frequently growth inhibitory for lymphocytes and induce apoptosis in cortical thymocytes by regulating gene expression. In the present study, immediate early gene expression was examined in WEHI7.2 thymoma cells undergoing cAMP-mediated apoptosis. Temporal differences in c-fos, junB, and inducible cAMP early repressor (ICER) steady-state mRNA levels were observed after forskolin exposure. Maximal induction of c-fos and junB occurred within 1 h, returning to basal levels by 3.5 h. In contrast, a 1.5-h time lag was observed before ICER transcript levels increased, reaching maximal levels after 3.5 h. This rise in expression, correlating with the decrease in c-fos and junB levels, preceded apoptotic DNA fragmentation by 1.5 h. Transient expression of ICER promoter constructs demonstrated that cAMP responsiveness occurred through cAMP-autoregulatory response element (CARE)3/4, two of the four proposed response elements in the ICER promoter. In contrast to the cAMP-responsive cell line JEG-3, CARE1/2 was not functional for cAMP-activated transcription in WEHI7.2 cells. An observed differential binding pattern of WEHI and JEG nuclear extracts to these elements may account for the cell-speci...Continue Reading

Citations

Apr 15, 2004·Molecular and Cellular Biology·Ghia EuskirchenMichael Snyder
Jul 12, 2003·Circulation Research·Mark A Sussman
Oct 18, 2018·Journal of Cancer Research and Clinical Oncology·Qiang LiWei-Xi Shen
Sep 22, 2005·Journal of Neuroscience Research·Corinne M SpencerThomas A Houpt
Oct 19, 1999·Molecular and Cellular Biology·M UbedaJ F Habener
May 9, 2000·The Journal of Biological Chemistry·D A KruegerD R Dowd

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