Regulation of the orphan receptor TR3 nuclear functions by c-Jun N terminal kinase phosphorylation
Autor: | Qiao Wu, Jia-fa Wu, Yan-yan Zhan, Xiao-yan Zhang, Bo Liu, Hang-zi Chen |
---|---|
Rok vydání: | 2006 |
Předmět: |
Receptors
Steroid p38 mitogen-activated protein kinases Biology Kidney environment and public health MAP2K7 Phosphorylation cascade Cell Line Endocrinology Nuclear Receptor Subfamily 4 Group A Member 1 Serine Humans Phosphorylation Luciferases Cell Nucleus Receptors Thyroid Hormone MAP kinase kinase kinase Kinase c-jun JNK Mitogen-Activated Protein Kinases Molecular biology DNA-Binding Proteins enzymes and coenzymes (carbohydrates) Gene Expression Regulation Mitogen-activated protein kinase biology.protein Mitogens Cell Division |
Zdroj: | Endocrinology. 148(1) |
ISSN: | 0013-7227 |
Popis: | The orphan receptor TR3 functions in the nucleus as a transcription factor to negatively or positively regulate gene expression. c-Jun N-terminal kinase (JNK) phosphorylation plays an important role in modulating the nuclear functions of TR3. Although TR3 is the phosphorylation target of JNK, the regulatory mechanism of JNK on TR3 functions remains to be elucidated. Here we showed that JNK activator anisomycin induced TR3 phosphorylation through JNK1 rather than p38 and ERK signals, which is mediated by its upstream factors MAPK kinase 4 and MAPK kinase 7. We also identified the exact phosphorylation site of JNK to be serine 95 at the N terminus of TR3, around which a classical JNK phosphorylation motif exists. Furthermore, we demonstrated that TR3 phosphorylation by JNK coincided with its ubiquitination and degradation, resulting in the loss of its mitogenic activity. Finally, we showed that JNK-induced phosphorylation blocked the DNA binding property of TR3 and hence diminished its transactivation activity. Taken together, our findings revealed a novel cross talk between TR3 and JNK signal pathway and shed light on the mechanism of JNK phosphorylation-dependent regulation on TR3 nuclear functions. |
Databáze: | OpenAIRE |
Externí odkaz: |