|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print December 23, 2004
Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582
Corresponding Author: tmuta{at}mailserver.med.kyushu-u.ac.jp
I
J. Biol. Chem, 10.1074/jbc.M412738200
Submitted on November 10, 2004
Revised on December 20, 2004
Accepted on December 23, 2004
Positive and negative regulation of nuclear factor-
B-mediated transcription by I
B-
, an inducible nuclear protein
B-
is an inducible nuclear protein that interacts with nuclear factor-
B (NF-
B) via its carboxyl-terminal ankyrin-repeats. Previous studies using an NF-
B reporter have shown that I
B-
inhibits the activity of NF-
B. In the present study, we dissected the N-terminal region of I
B-
, which shows no homology to any other proteins. Indirect immunofluorescence studies demonstrated the presence of a bipartite nuclear localization signal spanning amino acids 163-178. Using GAL4-fusion proteins, we found that internal fragments containing amino acids 329-402 possessed intrinsic transcriptional activation activity. Interestingly, the activity was not detected in GAL4-fusion proteins of the full-length I
B-
. On the other hand, the GAL4-dependent transcriptional activity was generated by co-expression of the GAL4-NF-
B p50 subunit fusion protein and the full-length I
B-
, neither of which exhibited the activity on their own. A new splicing variant, I
B-
(D), with a deletion of amino acids 236-429, was found to lack transactivation activity. Forced expression of I
B-
, but not I
B-
(D), augmented interleukin-6 production, indicating the functional significance of the transactivation activity. In contrast, tumor necrosis factor-
production was inhibited by expression of I
B-
, highlighting the dual functions of this molecule. These results indicate that I
B-
harbors latent transcriptional activation activity, and that the activity is expressed upon interaction with the NF-
B p50 subunit. In addition to the inhibitory activity on NF-
B-mediated transcription, the transcriptional activation activity of I
B-
should be crucial for the regulation of inflammation.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
G. Lenz, G. W. Wright, N. C. T. Emre, H. Kohlhammer, S. S. Dave, R. E. Davis, S. Carty, L. T. Lam, A. L. Shaffer, W. Xiao, et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways PNAS, September 9, 2008; 105(36): 13520 - 13525. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Kayama, V. R. Ramirez-Carrozzi, M. Yamamoto, T. Mizutani, H. Kuwata, H. Iba, M. Matsumoto, K. Honda, S. T. Smale, and K. Takeda Class-specific Regulation of Pro-inflammatory Genes by MyD88 Pathways and I{kappa}B{zeta} J. Biol. Chem., May 2, 2008; 283(18): 12468 - 12477. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. E. Simmonds and B. M. Foxwell Signalling, inflammation and arthritis: NF-{kappa}B and its relevance to arthritis and inflammation Rheumatology, May 1, 2008; 47(5): 584 - 590. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.S. Knox and J.C. Baker Genome-wide expression profiling of placentas in the p57Kip2 model of pre-eclampsia Mol. Hum. Reprod., April 1, 2007; 13(4): 251 - 263. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Totzke, F. Essmann, S. Pohlmann, C. Lindenblatt, R. U. Janicke, and K. Schulze-Osthoff A Novel Member of the I{kappa}B Family, Human I{kappa}B-{zeta}, Inhibits Transactivation of p65 and Its DNA Binding J. Biol. Chem., May 5, 2006; 281(18): 12645 - 12654. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B. Cowland, T. Muta, and N. Borregaard IL-1beta-Specific Up-Regulation of Neutrophil Gelatinase-Associated Lipocalin Is Controlled by I{kappa}B-{zeta} J. Immunol., May 1, 2006; 176(9): 5559 - 5566. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. A. Frost, G. J. Nystrom, and C. H. Lang Multiple Toll-like receptor ligands induce an IL-6 transcriptional response in skeletal myocytes Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R773 - R784. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |