Beta-catenin translocates to the nucleus

Stable Identifier
Reaction [omitted]
Homo sapiens
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Although it is well established that stabilized beta-catenin is translocated to the nucleus upon WNT pathway activation, the mechanisms that control beta-catenin localization are not fully elucidated. Beta-catenin has neither an NLS nor an NES, and its localization likely arises as the result of a complicated balance between shuttling and retention in both the nucleus and the cytoplasm (reviewed in MacDonald et al, 2009, Saito-Diaz et al, 2013). Nuclear entry of beta-catenin is independent of importins and RanGTPase (Fagotto et al, 1998; Yokoya et al, 1999) and beta-catenin has been suggested to interact directly with the nuclear pore complex by virtue of the structural similarity of its ARM domains to the importin-beta HEAT repeats (Kutay et al, 1997; Malik et al, 1997). Beta-catenin may also 'piggy-back' into the nucleus in complex with other proteins such as FOXM1 (Zhang et al, 2011 ) or BCL9 (Townsley et al, 2004). Once in the nucleus, interaction with TCF, BCL9 and Pygopus may function as an anchor for beta-catenin (Tolwinski and Wieschaus, 2001; Townsley et al, 2004; Krieghoff et al, 2006). Many of the components of the destruction complex, including APC and AXIN are also found in the nucleus and are thought to contribute to beta-catenin localization (Henderson and Fagotto, 2002; Cong and Varmus, 2004). Finally, recent work has revealed a role for Rac1 GTPase and Jun N-terminal kinase 2 (JNK2) in the nuclear localization of beta-catenin upon WNT pathway activation, although the mechanism for this remains to be elucidated (Wu et al, 2008).

Literature References
PubMed ID Title Journal Year
15208637 Pygopus and Legless target Armadillo/beta-catenin to the nucleus to enable its transcriptional co-activator function

Townsley, FM, Cliffe, A, Bienz, M

Nat Cell Biol 2004
16554443 Nucleo-cytoplasmic distribution of beta-catenin is regulated by retention

Krieghoff, E, Behrens, J, Mayr, B

J Cell Sci 2006
18423204 Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling

Wu, X, Tu, X, Joeng, KS, Hilton, MJ, Williams, DA, Long, F

Cell 2008
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
9391096 Evolutionary specialization of the nuclear targeting apparatus

Malik, HS, Eickbush, TH, Goldfarb, DS

Proc. Natl. Acad. Sci. U.S.A. 1997
12223464 The ins and outs of APC and beta-catenin nuclear transport

Henderson, BR, Fagotto, F

EMBO Rep. 2002
9135132 Dominant-negative mutants of importin-beta block multiple pathways of import and export through the nuclear pore complex

Kutay, U, Izaurralde, E, Bischoff, FR, Mattaj, IW, Görlich, D

EMBO J. 1997
22014570 FoxM1 promotes ?-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis

Zhang, N, Wei, P, Gong, A, Chiu, WT, Lee, HT, Colman, H, Huang, H, Xue, J, Liu, M, Wang, Y, Sawaya, R, Xie, K, Yung, WK, Medema, RH, He, X, Huang, S

Cancer Cell 2011
11493532 Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan

Tolwinski, NS, Wieschaus, E

Development 2001
9501980 Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin

Fagotto, F, Glück, U, Gumbiner, BM

Curr. Biol. 1998
14981260 Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin

Cong, F, Varmus, H

Proc. Natl. Acad. Sci. U.S.A. 2004
10198061 beta-catenin can be transported into the nucleus in a Ran-unassisted manner

Yokoya, F, Imamoto, N, Tachibana, T, Yoneda, Y

Mol. Biol. Cell 1999
19619488 Wnt/beta-catenin signaling: components, mechanisms, and diseases

MacDonald, BT, Tamai, K, He, X

Dev Cell 2009
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Orthologous Events