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XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization.
- Source :
-
Molecular cell [Mol Cell] 2007 Jun 08; Vol. 26 (5), pp. 689-702. - Publication Year :
- 2007
-
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.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Amino Acid Sequence
Animals
Apoptosis Regulatory Proteins
Cell Line
Cells, Cultured
Crystallography, X-Ray
Dimerization
Humans
In Vitro Techniques
Intracellular Signaling Peptides and Proteins chemistry
Intracellular Signaling Peptides and Proteins genetics
Intracellular Signaling Peptides and Proteins metabolism
Mice
Mitochondrial Proteins metabolism
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes
Phosphorylation
Protein Structure, Tertiary
Recombinant Fusion Proteins chemistry
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Sequence Homology, Amino Acid
Static Electricity
Surface Plasmon Resonance
X-Linked Inhibitor of Apoptosis Protein genetics
Adaptor Proteins, Signal Transducing chemistry
Adaptor Proteins, Signal Transducing metabolism
NF-kappa B metabolism
X-Linked Inhibitor of Apoptosis Protein chemistry
X-Linked Inhibitor of Apoptosis Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-2765
- Volume :
- 26
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 17560374
- Full Text :
- https://doi.org/10.1016/j.molcel.2007.05.006