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

J. Biol. Chem., Vol. 280, Issue 32, 29233-29241, August 12, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/32/29233    most recent M501670200v1 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 Hu, W.-H. Articles by Bethea, J. R. Search for Related Content PubMed PubMed Citation Articles by Hu, W.-H. Articles by Bethea, J. R. Social Bookmarking                      What's this?

NIBP, a Novel NIK and IKK-binding Protein That Enhances NF-B Activation^*

Wen-Hui Hu¶||, Julie S. Pendergast**¶, Xian-Ming Mo, Roberta Brambilla, Valerie Bracchi-Ricard, Fang Li, Winston M. Walters, Bas Blits, Li He, Sandra M. Schaal**, and John R. Bethea**

From the The Miami Project to Cure Paralysis, Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, Florida 33136, the ^**Neuroscience Program, Miller School of Medicine, University of Miami, Miami, Florida 33136, the Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China, and the Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298

The transcription factor NF-B plays an important role in both physiological and pathological events in the central nervous system. Nevertheless, the mechanisms of NF-B-mediated regulation of gene expression, and the signaling molecules participating in the NF-B pathway in the central nervous system are, to date, poorly understood. To identify such molecules, we conducted a yeast two-hybrid screen of a human brain cDNA library using NIK as bait. As a result, we identified a novel NIK and IKK binding protein designated NIBP that is mainly expressed in brain, muscle, heart, and kidney. Interestingly, low levels of expression were detected in immune tissues such as spleen, thymus, and peripheral blood leukocytes, where NF-B is known to modulate immune function. We demonstrated by immunohistochemistry that NIBP expression in the brain is localized to neurons. NIBP physically interacts with NIK, IKK, but not IKK or IKK. NIBP overexpression potentiates tumor necrosis factor--induced NF-B activation through increased phosphorylation of the IKK complex and its downstream IB and p65 substrates. Finally, knockdown of NIBP expression by small interfering RNA reduces tumor necrosis factor--induced NF-B activation, prevents nerve growth factor-induced neuronal differentiation, and decreases Bcl-xL gene expression in PC12 cells. Our data demonstrate that NIBP, by interacting with NIK and IKK, is a new enhancer of the cytokine-induced NF-B signaling pathway. Because of its neuronal expression, we propose that NIBP may be a potential target for modulating the NF-B signaling cascade in neuronal pathologies dependent upon abnormal activation of this pathway.

Received for publication, February 14, 2005 , and in revised form, May 18, 2005.

^* This work was supported by the National Institutes of Health Grant NS37130 (to J. R. B.) and The Miami Project to Cure Paralysis. 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.

^¶ Both are considered co-first authors.

^|| To whom correspondence may be addressed: Dept. of Physiology, Medical College of Virginia, VA Commonwealth University, Sanger Hall, Rm. 12-002, 1101 East Marshall St., Richmond, VA 23298. Tel.: 804-828-8504; Fax: 804-828-2500; E-mail: whu{at}vcu.edu.

To whom correspondence may be addressed: The Miami Project To Cure paralysis, Miller School of Medicine, University of Miami, 1095 NW 14th Terrace, Miami, FL 33136. Tel.: 305-243-3804; Fax: 305-243-3914; E-mail: JBethea{at}miami.edu.

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

This article has been cited by other articles:

				R. L. Austin, A. Rune, K. Bouzakri, J. R. Zierath, and A. Krook siRNA-Mediated Reduction of Inhibitor of Nuclear Factor-{kappa}B Kinase Prevents Tumor Necrosis Factor-{alpha}-Induced Insulin Resistance in Human Skeletal Muscle Diabetes, August 1, 2008; 57(8): 2066 - 2073. [Abstract] [Full Text] [PDF]

				C. W. Ross, P. D. Ouillette, C. M. Saddler, K. A. Shedden, and S. N. Malek Comprehensive Analysis of Copy Number and Allele Status Identifies Multiple Chromosome Defects Underlying Follicular Lymphoma Pathogenesis Clin. Cancer Res., August 15, 2007; 13(16): 4777 - 4785. [Abstract] [Full Text] [PDF]