PMID- 10336492
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 22
DP  - 1999 May 28
TI  - Transient nuclear factor kappaB (NF-kappaB) activation stimulated by
      interleukin-1beta may be partly dependent on proteasome activity, but not
      phosphorylation and ubiquitination of the IkappaBalpha molecule, in C6 glioma
      cells. Regulation of NF-kappaB linked to chemokine production.
PG  - 15875-82
AB  - We previously reported that several stresses can induce cytokine-induced
      neutrophil chemoattractant expression in a nuclear factor kappaB
      (NF-kappaB)-dependent manner. In this study, we focused further on the regulation
      of NF-kappaB. The activation of NF-kappaB and the subsequent cytokine-induced
      neutrophil chemoattractant induction in response to interleukin-1beta (IL-1beta) 
      were inhibited by proteasome inhibitors, MG132 and proteasome inhibitor I.
      Translocation of NF-kappaB into nuclei occurs by the phosphorylation,
      multi-ubiquitination, and degradation of IkappaBalpha, a regulatory protein of
      NF-kappaB. Nascent IkappaBalpha began to degrade 5 min after treatment with
      IL-1beta and disappeared completely after 15 min. However, IkappaBalpha returned 
      to basal levels after 45-60 min. Interestingly, resynthesized IkappaBalpha was
      already phosphorylated at Ser-32. These results suggest that 1) the upstream
      signals are still activated, although the translocation of NF-kappaB peaks at 15 
      min; and 2) the regulated protein(s) acts downstream of IkappaBalpha
      phosphorylation. Western blotting showed that the resynthesized and
      phosphorylated IkappaB molecules were also upward-shifted by multi-ubiquitination
      in response to IL-1beta treatment. On the other hand, ATP-dependent
      Leu-Leu-Val-Tyr cleaving activity transiently increased, peaked at 15 min, and
      then decreased to basal levels at 60 min. Furthermore, the cytosolic fraction
      that was stimulated by IL-1beta for 15 min, but not for 0 and 60 min, could
      degrade phosphorylated and multi-ubiquitinated IkappaBalpha. These results
      indicate that the transient translocation of NF-kappaB in response to IL-1beta
      may be partly dependent on transient proteasome activation.
FAU - Uehara, T
AU  - Uehara T
AD  - Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido 
      University, Sapporo 060-0812, Japan.
FAU - Matsuno, J
AU  - Matsuno J
FAU - Kaneko, M
AU  - Kaneko M
FAU - Nishiya, T
AU  - Nishiya T
FAU - Fujimuro, M
AU  - Fujimuro M
FAU - Yokosawa, H
AU  - Yokosawa H
FAU - Nomura, Y
AU  - Nomura Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Benzoquinones)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Chemotactic Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Growth Substances)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-1)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Leupeptins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, rat)
RN  - 0 (Oligopeptides)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Quinones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ubiquitins)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 1W306TDA6S (Rifabutin)
RN  - 70563-58-5 (herbimycin)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
SB  - IM
MH  - Animals
MH  - Benzoquinones
MH  - *Chemokines, CXC
MH  - Chemotactic Factors/genetics
MH  - Cysteine Endopeptidases/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Activation
MH  - Gene Expression Regulation/drug effects
MH  - Glioma
MH  - Growth Substances/genetics
MH  - *I-kappa B Proteins
MH  - *Intercellular Signaling Peptides and Proteins
MH  - Interleukin-1/*metabolism
MH  - Lactams, Macrocyclic
MH  - Leupeptins/pharmacology
MH  - Multienzyme Complexes/*metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism
MH  - Oligopeptides/metabolism
MH  - Phosphorylation
MH  - Protease Inhibitors/pharmacology
MH  - Proteasome Endopeptidase Complex
MH  - Quinones/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rifabutin/analogs & derivatives
MH  - Transcriptional Activation/drug effects
MH  - Tumor Cells, Cultured
MH  - Ubiquitins/*metabolism
EDAT- 1999/05/21 00:00
MHDA- 1999/05/21 00:01
CRDT- 1999/05/21 00:00
PHST- 1999/05/21 00:00 [pubmed]
PHST- 1999/05/21 00:01 [medline]
PHST- 1999/05/21 00:00 [entrez]
AID - 10.1074/jbc.274.22.15875 [doi]
AID - S0021-9258(19)73101-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 May 28;274(22):15875-82. doi: 10.1074/jbc.274.22.15875.