Induction of beta-transducin repeat-containing protein by JNK signaling and its role in the activation of NF-kappaB
| Autor: | Thomas J. Slaga, Ze'ev Ronai, Vladimir S. Spiegelman, Michele Pagano, Serge Y. Fuchs, Esther Latres, Pete Stavropoulos |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
p38 mitogen-activated protein kinases
Molecular Sequence Data IκB kinase Biochemistry Cell Line chemistry.chemical_compound Mice Ubiquitin GTP-Binding Proteins Animals Humans Amino Acid Sequence RNA Messenger Molecular Biology Transcription factor biology Kinase JNK Mitogen-Activated Protein Kinases NF-kappa B NF-κB Cell Biology 3T3 Cells beta-Transducin Repeat-Containing Proteins Ubiquitin ligase Cell biology chemistry Immunology biology.protein Phosphorylation Mitogen-Activated Protein Kinases Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 276(29) |
| ISSN: | 0021-9258 |
| Popis: | Activation of Jun N-kinase (JNK) and NF-kappaB transcription factor are the hallmarks of cellular response to stress. Phosphorylation of NF-kappaB inhibitor (IkappaB) by respective stress-inducible kinases (IKK) is a key event in NF-kappaB activation. beta-TrCP F-box protein mediates ubiquitination of phosphorylated IkappaB via recruitment of SCF(beta-TrCP)-Roc1 E3 ubiquitin ligase complex. Subsequent proteasome-dependent degradation of IkappaB results in activation of the NF-kappaB pathway. We found that a variety of cellular stress stimuli induce an increase in the steady state levels of beta-TrCP mRNA and protein levels in human cells. Activation of stress-activated protein kinases JNK (and, to a lesser extent, p38) by forced expression of constitutively active mutants of JNKK2 and MKK6 (but not MEK1 or IKKbeta) also leads to accumulation of beta-TrCP. Transcription of the beta-TrCP gene is not required for JNK-mediated induction of beta-TrCP. A synergistic effect of stimulation of IKK and JNK on the transcriptional activity of NF-kappaB was observed. The mechanisms of beta-TrCP induction via stress and its role in NF-kappaB activation are discussed. |
| Databáze: | OpenAIRE |
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