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Functional interaction of Jun and homeodomain proteins
L K Schaefer1, S Wang, T S Schaefer
1Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
The Journal of Biological Chemistry
|September 12, 2001
Summary
The homeodomain protein Hex interacts with the N-terminal region of c-Jun, inhibiting transcription. This interaction between Jun and homeodomain proteins may regulate developmental programs.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- c-Jun N-terminal region is involved in regulatory interactions.
- Homeodomain proteins are critical regulators of development.
- Jun and homeodomain proteins both regulate the basic fibroblast growth factor gene.
Purpose of the Study:
- Identify proteins interacting with the c-Jun N-terminal region.
- Investigate the functional consequences of Hex-Jun interactions.
- Explore the role of Jun and homeodomain family interactions in gene regulation.
Main Methods:
- Yeast two-hybrid system to identify interacting proteins.
- Site-directed mutagenesis to analyze Hex homeodomain interaction domains.
- Reporter gene assays in transfected cells to assess transcriptional regulation.
- Analysis of Jun-dependent transcription of the basic fibroblast growth factor gene.
Main Results:
- The homeodomain protein Hex interacts with the N-terminal region of c-Jun.
- Hex homeodomain is sufficient for interaction, with mutations in helix III reducing binding.
- Hex inhibits Jun/c-Fos-dependent transcription, an effect enhanced by Hex-binding sites.
- Hex expression significantly reduces Jun-dependent transcription of the basic fibroblast growth factor gene.
- Expression of Drosophila ultrabithorax enhances c-Jun-dependent transcription.
Conclusions:
- Functional interactions between Jun and homeodomain proteins are identified.
- Hex acts as a repressor of Jun-mediated transcription.
- These interactions suggest a critical role in regulating developmental and differentiation programs.
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