Abstract
The JunD transcription factor is one member of the Jun family of proteins that also includes c-Jun and JunB. Although c-Jun can function to promote cell proliferation and can cooperate with other oncogenes to transform cells, JunD slows proliferation of fibroblasts and antagonizes transformation by activated ras. Two isoforms of JunD, a full-length isoform containing 341 amino acids (JunD-FL) and a truncated isoform lacking 48 amino acids at the N terminus (Delta JunD), are generated through utilization of two translation start sites within a single mRNA. Here we show that both isoforms of JunD are phosphorylated by Jun N-terminal kinases (JNKs) at three identical residues and that both contain a docking domain that specifically binds JNKs. The JunD-FL isoform binds to and is phosphorylated by JNK more efficiently than Delta JunD in vitro; correspondingly, JunD-FL is a more potent transcriptional activator than Delta JunD. Although increased JNK signaling can activate both JunD isoforms, mutating either the JNK docking domain or the target JNK phosphorylation sites blocks this activation. These results identify two distinct isoforms of JunD with differential responses to JNK signaling pathways.
Highlights
The AP-1 transcription factor consists of a large set of dimer combinations formed between the Jun, Fos, and ATF families of proteins [1,2,3]
We have characterized a functional Jun N-terminal kinases (JNKs) docking domain present in both JunD isoforms and identified amino acid residues that are essential for JNK docking activity
The Jun family of proteins and AP-1 transcriptional activity are implicated in a variety of biological phenomena ranging from cell proliferation and transformation to apoptosis and development [9, 11,12,13, 45]
Summary
The AP-1 transcription factor consists of a large set of dimer combinations formed between the Jun, Fos, and ATF families of proteins [1,2,3]. Identification of JNK Target Residues in JunD Isoforms—To further confirm that there were no additional JNK target sites within the first 48 amino acids of JunD, we compared phosphopeptide maps of the GST fusion proteins that were phosphorylated in vitro by JNK (Fig. 3B).
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