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Xiap induces nf-kappa b activation via the bir1/tab1 interaction and bir1 dimerization

Academic Article
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Overview

authors

  • Lu, M.
  • Lin, S. C.
  • Huang, Y. H.
  • Kang, Young Jun
  • Rich, R.
  • Lo, Y. C.
  • Myszka, D.
  • Han, Jiahuai
  • Wu, H.

publication date

  • June 2007

journal

  • Molecular Cell  Journal

abstract

  • In addition to caspase inhibition, X-linked inhibitor of apoptosis (XIAP) induces NF-kappaB 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-kappaB activation. TAB1 is an upstream adaptor for the activation of the kinase TAK1, which in turn couples to the NF-kappaB 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-kappaB 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-kappaB activation, implicating a proximity-induced mechanism for TAK1 activation.

subject areas

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cells, Cultured
  • Crystallography, X-Ray
  • Dimerization
  • Humans
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mitochondrial Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes
  • NF-kappa B
  • Phosphorylation
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins
  • Sequence Homology, Amino Acid
  • Static Electricity
  • Surface Plasmon Resonance
  • X-Linked Inhibitor of Apoptosis Protein
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Identity

PubMed Central ID

  • PMC1991276

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2007.05.006

PubMed ID

  • 17560374
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Additional Document Info

start page

  • 689

end page

  • 702

volume

  • 26

issue

  • 5

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