Regulation of two JunD isoforms by Jun N-terminal kinases.
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.
Yazgan
Oya
O
Department of Cell Biology and Biochemistry and the Southwest Cancer Center at University Medical Center, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
Pfarr
Curt M
CM
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases