APC truncation mutants have impaired AXIN binding

Stable Identifier
R-HSA-4791278
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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APC truncation mutants have impaired AXIN binding
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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
10749138 The beta-catenin binding domain of adenomatous polyposis coli is sufficient for tumor suppression

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

Cancer Res. 2000
8757136 Functional interaction of beta-catenin with the transcription factor LEF-1

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

Nature 1996
11522655 Suppression of beta-catenin inhibits the neoplastic growth of APC-mutant colon cancer cells

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

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

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

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

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

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

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

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

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

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

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

Kinzler, KW, Vogelstein, B, Su, LK

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

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

Science 1993
Participants
Input
Participates
as an event of
Normal reaction
Assembly of the destruction complex (Homo sapiens)
Functional status

Loss of function of APC truncation mutants [cytosol]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
colorectal cancer DOID:9256
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2013-10-07)
Reviewed
Salahshor, S  (2014-05-12)
Woodgett, J  (2014-05-22)
Created
Rothfels, K  (2013-10-28)
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