1luj
|
Crystal Structure of the Beta-catenin/ICAT Complex
OverviewOverview
Beta-catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. Transcription mediated by the beta-catenin/Tcf complex is involved in embryological development and is upregulated in various cancers. We have determined the crystal structure at 2.5 A resolution of a complex between beta-catenin and ICAT, a protein that prevents the interaction between beta-catenin and Tcf/Lef family transcription factors. ICAT contains a 3-helix bundle that binds armadillo repeats 10-12 and a C-terminal tail that, similar to Tcf and E-cadherin, binds in the groove formed by armadillo repeats 5-9 of beta-catenin. We show that ICAT selectively inhibits beta-catenin/Tcf binding in vivo, without disrupting beta-catenin/cadherin interactions. Thus, it should be possible to design cancer therapeutics that inhibit beta-catenin-mediated transcriptional activation without interfering with cell adhesion.
DiseaseDisease
Known diseases associated with this structure: Colorectal cancer OMIM:[116806], Hepatoblastoma OMIM:[116806], Hepatocellular carcinoma OMIM:[116806], Ovarian carcinoma, endometrioid type OMIM:[116806], Pilomatricoma OMIM:[116806]
About this StructureAbout this Structure
1LUJ is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT., Graham TA, Clements WK, Kimelman D, Xu W, Mol Cell. 2002 Sep;10(3):563-71. PMID:12408824
Page seeded by OCA on Thu Feb 21 13:48:34 2008