Regulation of Two JunD Isoforms by Jun N-terminal Kinases

Oya Yazgan, Curt M. Pfarr
2002 Journal of Biological Chemistry  
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 (⌬JunD), are generated through
more » ... ted 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 ⌬JunD in vitro; correspondingly, JunD-FL is a more potent transcriptional activator than ⌬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.
doi:10.1074/jbc.m204552200 pmid:12052834 fatcat:dzkgjdrzsjgjrbg7m43nok26tm