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Control of c-Jun activity by interaction of a cell-specific inhibitor with regulatory domain delta: differences
1Howard Hughes Medical Institute, University of California, Berkeley 94720.
Abstract:
Analysis of transcriptional activation properties of c-Jun chimeras in different cell lines suggests that it contains an activator domain (A1) that is negatively regulated by a cell type-specific inhibitor. A regulatory domain of c-Jun, delta, previously identified by in vitro experiments, also regulates transcriptional activation by c-Jun in vivo. The delta domain facilitates or stabilizes the interaction of the cellular inhibitor with A1. v-Jun, which lacks delta, is a stronger transcriptional activator than c-Jun, since its activity is not efficiently repressed by the cellular inhibitor. In vitro transcription with chimeric Jun proteins and extracts from different cell types confirms that the A1 and delta domains are repressed in a cell type-specific manner. These findings implicate a specific cellular factor in the negative regulation of c-Jun activity and suggest a molecular basis for the observed difference in transcriptional properties between v-Jun and c-Jun.
Insights
Cellular inhibitors negatively regulate c-Jun transcriptional activity via the A1 domain, with the delta domain mediating this repression. This explains why v-Jun, lacking delta, is a stronger activator than c-Jun.
Area of Science:
- Molecular Biology
- Gene Regulation
- Cellular Signaling
Background:
- c-Jun is a transcription factor involved in various cellular processes.
- Transcriptional activity of c-Jun can be modulated by regulatory domains.
- Differences in transcriptional properties exist between c-Jun and its viral counterpart, v-Jun.
Purpose of the Study:
- To investigate the transcriptional activation properties of c-Jun.
- To identify the regulatory mechanisms controlling c-Jun activity in vivo.
- To elucidate the role of the delta domain in c-Jun regulation.
Main Methods:
- Analysis of c-Jun chimeras in different cell lines.
- In vitro transcription assays using chimeric Jun proteins and cell extracts.
- Investigating the interaction between regulatory domains and cellular inhibitors.
Main Results:
- c-Jun possesses an activator domain (A1) negatively regulated by a cell type-specific inhibitor.
- The delta domain of c-Jun facilitates the interaction between the inhibitor and A1.
- v-Jun, lacking the delta domain, exhibits stronger transcriptional activation due to reduced repression.
- Both A1 and delta domains are subject to cell type-specific repression.
Conclusions:
- A specific cellular factor negatively regulates c-Jun activity.
- The delta domain plays a crucial role in mediating cell type-specific repression of c-Jun.
- The findings provide a molecular explanation for the distinct transcriptional behaviors of c-Jun and v-Jun.
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