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Differential binding of the Menin tumor suppressor protein to JunD isoforms
1Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Abstract:
The role of the Jun family of proteins (c-Jun, JunB, and JunD) in oncogenesis has been extensively studied, but the distinct biological roles of each Jun protein is not known. For example, whereas c-Jun can transform primary cells in cooperation with an activated ras oncogene, JunD antagonizes ras-mediated transformation. We have discovered that two isoforms of the JunD transcription factor are ubiquitously expressed, resulting from use of an alternative translation start codon within the JunD mRNA. Here we report the first characterized functional difference between these JunD isoforms; only the full-length isoform of JunD binds to the Menin tumor suppressor protein. Furthermore, Menin suppresses transcriptional activity of the full-length but not the truncated isoform of JunD, which identifies the full-length JunD isoform as a functional target of Menin.
Insights
Two JunD protein isoforms exist, with only the full-length version binding the Menin tumor suppressor. Menin inhibits full-length JunD activity, identifying it as a functional target.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- The Jun protein family (c-Jun, JunB, JunD) plays a role in oncogenesis, but individual protein functions remain unclear.
- c-Jun promotes ras-mediated transformation, while JunD antagonizes it, suggesting distinct roles within the family.
Purpose of the Study:
- To investigate the distinct biological roles of JunD protein isoforms in oncogenesis.
- To characterize the functional differences between JunD isoforms and their interaction with the Menin tumor suppressor protein.
Main Methods:
- Discovered two ubiquitously expressed JunD transcription factor isoforms arising from alternative translation start codons.
- Identified differential binding of JunD isoforms to the Menin tumor suppressor protein.
- Assessed the effect of Menin on the transcriptional activity of both JunD isoforms.
Main Results:
- Two JunD isoforms, full-length and truncated, are ubiquitously expressed.
- Only the full-length JunD isoform binds to the Menin tumor suppressor protein.
- Menin suppresses the transcriptional activity of full-length JunD but not the truncated isoform.
Conclusions:
- The interaction between Menin and full-length JunD reveals a novel regulatory mechanism in oncogenesis.
- Full-length JunD is identified as a functional target of the Menin tumor suppressor protein.
- Understanding JunD isoform-specific functions and Menin interactions is crucial for cancer research.