Activation of Jun N-kinase (JNK) and NF-κB transcription factor are the hallmarks of cellular response to stress. Phosphorylation of NF-κB inhibitor (IκB) by respective stress-inducible kinases (IKK) is a key event in NF-κB activation. β-TrCP F-box protein mediates ubiquitination of phosphorylated Iκb via recruitment of SCF β-TrcP-Roc1 E3 ubiquitin ligase complex. Subsequent proteasome-dependent degradation of IκB results in activation of the NF-κB pathway. We found that a variety of cellular stress stimuli induce an increase in the steady state levels of β-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 IKKβ) also leads to accumulation of β-TrCP. Transcription of the β-TrCP gene is not required for JNK-mediated induction of β-TrCP. A synergistic effect of stimulation of IKK and JNK on the transcriptional activity of NF-κB was observed. The mechanisms of β-TrCP induction via stress and its role in NF-κB activation are discussed.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology