Induction of β-Transducin Repeat-containing Protein by JNK Signaling and Its Role in the Activation of NF-κB

Vladimir Spiegelman, Pete Stavropoulos, Esther Latres, Michele Pagano, Ze'Ev Ronai, Tomas J. Slaga, Serge Y. Fuchs

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27152-27158
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number29
DOIs
StatePublished - Jul 20 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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