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XIAP Induces NF-κB Activation via the BIR1/TAB1 Interaction and BIR1 Dimerization
- Source :
- Molecular Cell. 26:689-702
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 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 :
- Models, Molecular
Materials science
Recombinant Fusion Proteins
Molecular Sequence Data
Static Electricity
X-Linked Inhibitor of Apoptosis Protein
In Vitro Techniques
Crystallography, X-Ray
Inhibitor of apoptosis
Article
Cell Line
Mitochondrial Proteins
Mice
Animals
Humans
XIAP Deficiency
Amino Acid Sequence
Phosphorylation
Molecular Biology
Cells, Cultured
Caspase
Adaptor Proteins, Signal Transducing
Sequence Homology, Amino Acid
biology
Kinase
Intracellular Signaling Peptides and Proteins
NF-kappa B
Signal transducing adaptor protein
Cell Biology
Surface Plasmon Resonance
Protein Structure, Tertiary
Cell biology
XIAP
Multiprotein Complexes
Mitogen-activated protein kinase
biology.protein
Apoptosis Regulatory Proteins
Dimerization
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....62eb91c099290be4d836b1b2892d0235