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Title: XIAP Induces NF-kB Activation via the BIR1/TAB1 Interaction and BIR1 Dimerization

Abstract

In addition to caspase inhibition, X-linked inhibitor of apoptosis (XIAP) induces NF-{kappa}B and MAP kinase activation during TGF-b and BMP receptor signaling and upon overexpression. Here we show that the BIR1 domain of XIAP, which has no previously ascribed function, directly interacts with TAB1 to induce NF-{kappa}B activation. TAB1 is an upstream adaptor for the activation of the kinase TAK1, which in turn couples to the NF-{kappa}B pathway. We report the crystal structures of BIR1, TAB1, and the BIR1/TAB1 complex. The BIR1/TAB1 structure reveals a striking butterfly-shaped dimer and the detailed interaction between BIR1 and TAB1. Structure-based mutagenesis and knockdown of TAB1 show unambiguously that the BIR1/TAB1 interaction is crucial for XIAP-induced TAK1 and NF-{kappa}B activation. We show that although not interacting with BIR1, Smac, the antagonist for caspase inhibition by XIAP, also inhibits the XIAP/TAB1 interaction. Disruption of BIR1 dimerization abolishes XIAP-mediated NF-{kappa}B activation, implicating a proximity-induced mechanism for TAK1 activation.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930470
Report Number(s):
BNL-81222-2008-JA
Journal ID: ISSN 1097-2765; TRN: US200904%%737
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Molecular Cell; Journal Volume: 26; Journal Issue: 5
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; APOPTOSIS; ASPARTIC ACID; CRYSTAL STRUCTURE; CYSTEINE; DIMERIZATION; DIMERS; ENZYMES; INHIBITION; MUTAGENESIS; PHOSPHOTRANSFERASES; PROTEINS; RECEPTORS; national synchrotron light source

Citation Formats

Lu,M., Lin, S., Huang, Y., Kang, Y., Rich, R., Lo, Y., Myszka, D., Han, J., and Wu, H. XIAP Induces NF-kB Activation via the BIR1/TAB1 Interaction and BIR1 Dimerization. United States: N. p., 2007. Web. doi:10.1016/j.molcel.2007.05.006.
Lu,M., Lin, S., Huang, Y., Kang, Y., Rich, R., Lo, Y., Myszka, D., Han, J., & Wu, H. XIAP Induces NF-kB Activation via the BIR1/TAB1 Interaction and BIR1 Dimerization. United States. doi:10.1016/j.molcel.2007.05.006.
Lu,M., Lin, S., Huang, Y., Kang, Y., Rich, R., Lo, Y., Myszka, D., Han, J., and Wu, H. Mon . "XIAP Induces NF-kB Activation via the BIR1/TAB1 Interaction and BIR1 Dimerization". United States. doi:10.1016/j.molcel.2007.05.006.
@article{osti_930470,
title = {XIAP Induces NF-kB Activation via the BIR1/TAB1 Interaction and BIR1 Dimerization},
author = {Lu,M. and Lin, S. and Huang, Y. and Kang, Y. and Rich, R. and Lo, Y. and Myszka, D. and Han, J. and Wu, H.},
abstractNote = {In addition to caspase inhibition, X-linked inhibitor of apoptosis (XIAP) induces NF-{kappa}B and MAP kinase activation during TGF-b and BMP receptor signaling and upon overexpression. Here we show that the BIR1 domain of XIAP, which has no previously ascribed function, directly interacts with TAB1 to induce NF-{kappa}B activation. TAB1 is an upstream adaptor for the activation of the kinase TAK1, which in turn couples to the NF-{kappa}B pathway. We report the crystal structures of BIR1, TAB1, and the BIR1/TAB1 complex. The BIR1/TAB1 structure reveals a striking butterfly-shaped dimer and the detailed interaction between BIR1 and TAB1. Structure-based mutagenesis and knockdown of TAB1 show unambiguously that the BIR1/TAB1 interaction is crucial for XIAP-induced TAK1 and NF-{kappa}B activation. We show that although not interacting with BIR1, Smac, the antagonist for caspase inhibition by XIAP, also inhibits the XIAP/TAB1 interaction. Disruption of BIR1 dimerization abolishes XIAP-mediated NF-{kappa}B activation, implicating a proximity-induced mechanism for TAK1 activation.},
doi = {10.1016/j.molcel.2007.05.006},
journal = {Molecular Cell},
number = 5,
volume = 26,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}