HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 9, 7444-7451, March 4, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/9/7444    most recent M412738200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Motoyama, M. Articles by Muta, T. Search for Related Content PubMed PubMed Citation Articles by Motoyama, M. Articles by Muta, T. Social Bookmarking                      What's this?

Positive and Negative Regulation of Nuclear Factor-B-mediated Transcription by IB-, an Inducible Nuclear Protein^*

Masaiwa Motoyama, Soh Yamazaki, Akiko Eto-Kimura, Koichiro Takeshige, and Tatsushi Muta¶

From the Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan and the Host and Defense, PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan

IB- 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 IB- inhibits the activity of NF-B. In the present study, we dissected the amino-terminal region of IB-, 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 IB-. 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 IB-, neither of which exhibited the activity on their own. A new splicing variant, IB-(D), with a deletion of amino acids 236–429, was found to lack transactivation activity. Forced expression of IB-, but not IB-(D), augmented interleukin-6 production, indicating the functional significance of the transactivation activity. In contrast, tumor necrosis factor- production was inhibited by expression of IB-, highlighting the dual functions of this molecule. These results indicate that IB- 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 IB- should be crucial for the regulation of inflammation.

Received for publication, November 10, 2004 , and in revised form, December 20, 2004.

^* This work was supported in part by grants-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (to T. M., K. T., and S. Y.) and grants from the Naito Foundation (to T. M.) and the Kaibara Foundation (to T. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Figs. S1 and S2.

The nucleotide sequence(s) reported in this paper has been submitted to the DDBJ/GenBank^TM/EBI Data Bank with accession number(s) AB196497.

^¶ To whom all correspondence should be sent. Tel.: 81-92-642-6103; Fax: 81-92-642-6103; E-mail: tmuta{at}mailserver.med.kyushu-u.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				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]