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==Overview==

The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Wnt pathway leads, to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Wnt target genes. We have determined, the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 A, resolution. Our studies reveal that the beta-catenin binding site of BCL9, is distinct from that of most other beta-catenin partners and forms a good, target for developing drugs that block canonical Wnt/beta-catenin, signaling. The BCL9 beta-catenin binding domain (CBD) forms an alpha helix, that binds to the first armadillo repeat of beta-catenin, which can be, mutated to prevent beta-catenin binding to BCL9 without affecting cadherin, or alpha-catenin binding. We also demonstrate that beta-catenin Y142, phosphorylation, which has been proposed to regulate BCL9-2 binding, does, not directly affect the interaction of beta-catenin with either BCL9 or, BCL9-2.

The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Wnt pathway leads to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Wnt target genes. We have determined the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 A resolution. Our studies reveal that the beta-catenin binding site of BCL9 is distinct from that of most other beta-catenin partners and forms a good target for developing drugs that block canonical Wnt/beta-catenin signaling. The BCL9 beta-catenin binding domain (CBD) forms an alpha helix that binds to the first armadillo repeat of beta-catenin, which can be mutated to prevent beta-catenin binding to BCL9 without affecting cadherin or alpha-catenin binding. We also demonstrate that beta-catenin Y142 phosphorylation, which has been proposed to regulate BCL9-2 binding, does not directly affect the interaction of beta-catenin with either BCL9 or BCL9-2.

==Disease==

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[[Category: protein complex]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:32:44 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Wnt pathway leads, to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Wnt target genes. We have determined, the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 A, resolution. Our studies reveal that the beta-catenin binding site of BCL9, is distinct from that of most other beta-catenin partners and forms a good, target for developing drugs that block canonical Wnt/beta-catenin, signaling. The BCL9 beta-catenin binding domain (CBD) forms an alpha helix, that binds to the first armadillo repeat of beta-catenin, which can be, mutated to prevent beta-catenin binding to BCL9 without affecting cadherin, or alpha-catenin binding. We also demonstrate that beta-catenin Y142, phosphorylation, which has been proposed to regulate BCL9-2 binding, does, not directly affect the interaction of beta-catenin with either BCL9 or, BCL9-2.
+The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Wnt pathway leads to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Wnt target genes. We have determined the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 A resolution. Our studies reveal that the beta-catenin binding site of BCL9 is distinct from that of most other beta-catenin partners and forms a good target for developing drugs that block canonical Wnt/beta-catenin signaling. The BCL9 beta-catenin binding domain (CBD) forms an alpha helix that binds to the first armadillo repeat of beta-catenin, which can be mutated to prevent beta-catenin binding to BCL9 without affecting cadherin or alpha-catenin binding. We also demonstrate that beta-catenin Y142 phosphorylation, which has been proposed to regulate BCL9-2 binding, does not directly affect the interaction of beta-catenin with either BCL9 or BCL9-2.
 ==Disease==
@@ Line 20: / Line 20: @@
 [[Category: protein complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:28:28 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:32:44 2008''