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Structural basis of the Axin–adenomatous polyposis coli interaction
Author(s) -
Spink Katharine Eklof,
Polakis Paul,
Weis William I
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.10.2270
Subject(s) - biology , adenomatous polyposis coli , genetics , basis (linear algebra) , computational biology , colorectal cancer , cancer , geometry , mathematics
Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the absence of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto‐oncogene β‐catenin through the formation of a large complex containing these three proteins, glycogen synthase kinase 3β (GSK3β) and several other proteins. Both Axin and APC are known to be critical for β‐catenin regulation, and truncations in APC that eliminate the Axin‐binding site result in human cancers. A protease‐resistant domain of Axin that contains the APC‐binding site is a member of the regulators of G‐protein signaling (RGS) superfamily. The crystal structures of this domain alone and in complex with an Axin‐binding sequence from APC reveal that the Axin–APC interaction occurs at a conserved groove on a face of the protein that is distinct from the G‐protein interface of classical RGS proteins. The molecular interactions observed in the Axin–APC complex provide a rationale for the evolutionary conservation seen in both proteins.