Induction of beta-transducin repeat-containing protein by JNK signaling and its role in the activation of NF-kappa B

Activation of Jun N-kinase (JNK) and NF-kappaB transcription factor are the hallmarks of cellular response to stress. Phosphorylation of NF-kappaB inh ibitor (I kappaB) by respective stress-inducible kinases (IKK) is:a key eve nt in NF-kappaB activation. beta -TrCP F-box protein mediates ubiquitinatio n of phosphorylated I kappaB via recruitment of SCFbeta -TrCP-Roc1 E3 ubiqu itin Ligase complex. Subsequent proteasome-dependent degradation of I kappa B results in activation of the NF-kappaB pathway, We found that a variety o f cellular stress stimuli induce an increase in the steady state levels of beta -TrCP mRNA and protein levels in human cells. Activation of stress-act ivated protein kinases JNK (and, to a lesser extent, p38) by forced express ion of constitutively active mutants of JNKK2 and MKK6 (but not MEK1 or IKK beta) also leads to accumulation of beta -TrCP. Transcription of the beta -TrCP gene is not required for JNK-mediated induction of beta -TrCP. A syne rgistic effect of stimulation of IKK and JNK on the transcriptional activit y of NF-kappaB was observed. The mechanisms of beta -TrCP induction via str ess and its role in NF-kappaB activation are discussed.