APC truncation mutants have impaired AXIN binding

Stable Identifier
R-HSA-4791278
Type
Reaction [FailedReaction]
Species
Homo sapiens
Compartment
cytosol
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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
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
Participants
Input
Participant Of
hasEvent
Normal reaction
Assembly of the destruction complex (Homo sapiens)
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
colorectal cancer 9256
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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