Reactome | Beta-catenin translocates to the nucleus

Beta-catenin translocates to the nucleus

Stable Identifier

R-HSA-201669

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol, nucleoplasm

ReviewStatus

5/5

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Beta-catenin translocates to the nucleus

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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
19619488	Wnt/beta-catenin signaling: components, mechanisms, and diseases MacDonald, BT, Tamai, K, He, X	Dev Cell	2009
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
14981260	Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin Cong, F, Varmus, H	Proc. Natl. Acad. Sci. U.S.A.	2004
9501980	Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin Fagotto, F, Glück, U, Gumbiner, BM	Curr. Biol.	1998
11493532	Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan Tolwinski, NS, Wieschaus, E	Development	2001
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
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
12223464	The ins and outs of APC and beta-catenin nuclear transport Henderson, BR, Fagotto, F	EMBO Rep.	2002
9391096	Evolutionary specialization of the nuclear targeting apparatus Malik, HS, Eickbush, TH, Goldfarb, DS	Proc. Natl. Acad. Sci. U.S.A.	1997
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
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
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