Desch, Michael and Hackmayer, Gent and Todorov, Vladimir T. (2012) Identification of ATF2 as a transcriptional regulator of renin gene. BIOLOGICAL CHEMISTRY, 393 (1-2). pp. 93-100. ISSN 1431-6730,
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The cAMP response element (enhCRE) in the distal enhancer regulatory region of renin gene is believed to play a major role in the control of renin transcription. enhCRE binds the CRE-binding protein (CREB), which is the main transcription factor target of cAMP signaling. Using the mouse renin-producing cell line As4.1 we found that activating transcription factor-2 (ATF2) also binds to enhCRE. N-terminal phosphorylation of ATF2, which controls its transactivation, is associated with downregulation of renin gene expression by the cytokine tumor necrosis factor-alpha (TNF alpha). The ubiquitin proteasome inhibitor MG132 also phosphorylates ATF2 and inhibits renin expression. Knockdown of ATF2 attenuated the suppression of renin gene expression by MG132, thus demonstrating that ATF2 mediates the inhibitory effect of MG132. In addition, MG132 increased the DNA-binding of ATF2 as well as the ratio of bound ATF2 to CREB. Using ATF2- and CREB-Gal4 fusion protein constructs coupled with luciferase reporter system we showed that ATF2 has a weaker transactivating capacity than CREB. These data suggest that ATF2 represses renin expression by drifting the transcriptional control of renin gene away from CREB. Accordingly, TNF alpha completely abrogated the cAMP-dependent stimulation of renin gene expression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NECROSIS-FACTOR-ALPHA; AMP RESPONSE ELEMENT; ACTIVATING TRANSCRIPTION; EXPRESSION; BINDING; PHOSPHORYLATION; PROMOTER; CELLS; CREB; ATF2; CREB; gene expression; phosphorylation; renin; transcriptional repression |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 May 2020 08:07 |
| Last Modified: | 25 May 2020 08:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19540 |
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