APC truncation mutants have impaired AXIN binding

Stable Identifier
Reaction [transition]
Homo sapiens
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The tumor suppressor APC is a central component of the destruction complex that makes direct, functionally important contacts with a number of other destruction complex members, including AXIN, beta-catenin and GSK3 (Behrens et al, 1998; Kishida et al, 1998; Hart et al, 1998; Rubinfeld et al, 1993; Su et al, 1993; Rubinfeld et al, 1996). These protein-protein interactions are critical to APC's role in promoting the proteasome-mediated degradation of beta-catenin, and are abrogated by APC truncations that are common in the vast majority of colorectal cancers (reviewed in Saito-Diaz et al, 2013; Polakis, 2000; Polakis, 2012). Cancer cells with expressing truncated forms of APC have high levels of free beta-catenin and aberrant WNT target gene expression (Morin et al, 1997; Shih et al, 2000; Roh et al, 2001).

Literature References
PubMed ID Title Journal Year
8757136 Functional interaction of beta-catenin with the transcription factor LEF-1

Behrens, J, von Kries, JP, Kühl, M, Bruhn, L, Wedlich, D, Grosschedl, R, Birchmeier, W

Nature 1996
10749138 The beta-catenin binding domain of adenomatous polyposis coli is sufficient for tumor suppression

Shih, IM, Yu, J, He, TC, Vogelstein, B, Kinzler, KW

Cancer Res. 2000
11522655 Suppression of beta-catenin inhibits the neoplastic growth of APC-mutant colon cancer cells

Roh, H, Green, DW, Boswell, CB, Pippin, JA, Drebin, JA

Cancer Res. 2001
9065402 Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC

Morin, PJ, Sparks, AB, Korinek, V, Barker, N, Clevers, HC, Vogelstein, B, Kinzler, KW

Science 1997
22438566 Wnt signaling in cancer

Polakis, P

Cold Spring Harb Perspect Biol 2012
10921899 Wnt signaling and cancer

Polakis, P

Genes Dev. 2000
23256519 The way Wnt works: Components and mechanism

Saito-Diaz, K, Chen, TW, Wang, X, Thorne, CA, Wallace, HA, Page-McCaw, A, Lee, E

Growth Factors 2013
9601641 Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta

Hart, MJ, de los Santos, R, Albert, IN, Rubinfeld, B, Polakis, P

Curr. Biol. 1998
8638126 Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly

Rubinfeld, B, Albert, I, Porfiri, E, Fiol, C, Munemitsu, S, Polakis, P

Science 1996
9556553 Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin

Kishida, S, Yamamoto, H, Ikeda, S, Kishida, M, Sakamoto, I, Koyama, S, Kikuchi, A

J. Biol. Chem. 1998
8259519 Association of the APC tumor suppressor protein with catenins

Su, LK, Vogelstein, B, Kinzler, KW

Science 1993
8259518 Association of the APC gene product with beta-catenin

Rubinfeld, B, Souza, B, Albert, I, Müller, O, Chamberlain, SH, Masiarz, FR, Munemitsu, S, Polakis, P

Science 1993
Normal reaction
Functional status

Loss of function of APC truncation mutants [cytosol]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
colorectal cancer DOID:9256
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