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

J Biol Chem. 2001 Jul 20;276(29):27152-8. doi: 10.1074/jbc.M100031200. Epub 2001 May 24.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • GTP-Binding Proteins / biosynthesis*
  • GTP-Binding Proteins / genetics
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Signal Transduction*
  • beta-Transducin Repeat-Containing Proteins

Substances

  • BTRC protein, human
  • Btrc protein, mouse
  • NF-kappa B
  • RNA, Messenger
  • beta-Transducin Repeat-Containing Proteins
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • GTP-Binding Proteins