Functional characterization of two JunD isoforms



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Texas Tech University


The AP-1 transcription factor is involved in many diverse processes such as proliferation, transformation and apoptosis. The ability of AP-1 to rearrange its dimeric composition and DNA-binding activity allows for generation of numerous, highly specific signals. JunD is the predominant component of the AP-1 complex in nondividing cells and has the ability to slow down growth when overexpressed in cells. JunD mRNA generates two isoforms through the use of an alternative translational start site, the full-length isoform (JunD-FL) and a truncated form ΔJunD. We determined the role of two isoforms of JunD in their abilities to alter growth rate, to transactivate promoters, and to induce apoptosis. Our results indicate that JunD-FL has a higher transactivation potential than JunD and that overexpression of ΔJunD in mouse fibroblasts retards growth and sensitizes cells for apoptosis. We also examined their physical interactions with the Jun-N-terminal kinases (JNKs) and the tumor suppressor protein Menin. We found that only JunD-FL interacts with Menin and this interaction leads to inhibitton of the intrinsic transcriptional activity of JunD-FL. This finding suggests that two isoforms of the JunD transcriptions factor are differentially regulated. In addition, Menin inhibits the JNK-mediated acttvatton of both isoforms of JunD and c-Jun in transient transfection assays, suggesting that Menin could be involved in regulation of more diverse JNK substrates in the cell.



Transcription factors, Protein kinases, Jun oncogenes