2pop: Difference between revisions

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==Overview==

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.

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.

==Disease==

Known diseases associated with this structure: Lymphoproliferative syndrome, X-linked, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300079 300079]]

==About this Structure==

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[[Category: Homo sapiens]]

[[Category: Protein complex]]

[[Category: Lin, S.C.]]

[[Category: Lin, S C.]]

[[Category: ZN]]

[[Category: bir domain]]

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[[Category: zinc finger]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:31:41 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-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.
+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.
+==Disease==
+Known diseases associated with this structure: Lymphoproliferative syndrome, X-linked, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300079 300079]]
 ==About this Structure==
@@ Line 13: / Line 16: @@
 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
-[[Category: Lin, S.C.]]
+[[Category: Lin, S C.]]
 [[Category: ZN]]
 [[Category: bir domain]]
@@ Line 19: / Line 22: @@
 [[Category: zinc finger]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:40:58 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:31:41 2008''